Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma
The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair...
Saved in:
| Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 113; no. 8; pp. 2170 - 2175 |
|---|---|
| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
National Academy of Sciences
23.02.2016
National Acad Sciences |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0027-8424 1091-6490 1091-6490 |
| DOI | 10.1073/pnas.1525735113 |
Cover
Loading…
| Abstract | The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10−4), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel–Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10−17); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers. |
|---|---|
| AbstractList | The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10−4), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel–Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10−17); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers. Parts of clear cell renal cell carcinomas (ccRCCs) sometimes have histologic features characteristic of a sarcoma. So-called sarcomatoid tumors are more aggressive, difficult to treat, and associated with a poor prognosis. Their pathogenesis has been uncertain. Through separate exome sequencing of carcinomatous and sarcomatoid components, we show that these components share many somatic mutations, including many in genes characteristic of ccRCC. Sarcomatoid elements had significantly more new somatic mutations, particularly in cancer driver genes, than carcinomatous components. In particular, tumor protein p53, AT-rich interaction domain 1A, and BRCA1 associated protein 1 had sarcomatoid-specific homozygous mutation in 10 tumors and were all mutually exclusive, implicating these genes in sarcomatoid degeneration. The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10 −4 ), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel–Lindau tumor suppressor ( VHL ), polybromo 1 ( PBRM1 ), SET domain containing 2 ( SETD2 ), phosphatase and tensin homolog ( PTEN ). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 ( TP53 ) mutations in 32% of tumors ( P = 5.47 × 10 −17 ); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A ( ARID1A ) and BRCA1 associated protein 1 ( BAP1 ) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers. The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers.The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers. The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 x 10...), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 x 10...); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers. (ProQuest: ... denotes formulae/symbols omitted.) The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers. |
| Author | Merino, Maria J. Nawaf, Cayce B. Shuch, Brian Pantuck, Allan J. Zhao, Siming Lifton, Richard P. Bi, Mark Kluger, Harriet M. Xie, Zuoquan Bilgüvar, Kaya Said, Jonathan W. Choi, Jaehyuk Belldegrun, Arie S. Adeniran, Adebowale J. |
| Author_xml | – sequence: 1 givenname: Mark surname: Bi fullname: Bi, Mark organization: Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06511 – sequence: 2 givenname: Siming surname: Zhao fullname: Zhao, Siming organization: Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06511 – sequence: 3 givenname: Jonathan W. surname: Said fullname: Said, Jonathan W. organization: Department of Pathology, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095 – sequence: 4 givenname: Maria J. surname: Merino fullname: Merino, Maria J. organization: Translational Surgical Pathology Division, National Cancer Institute, Bethesda, MD 20850 – sequence: 5 givenname: Adebowale J. surname: Adeniran fullname: Adeniran, Adebowale J. organization: Department of Pathology, Yale School of Medicine, New Haven, CT 06511 – sequence: 6 givenname: Zuoquan surname: Xie fullname: Xie, Zuoquan organization: Department of Urology, Yale School of Medicine, New Haven, CT 06511 – sequence: 7 givenname: Cayce B. surname: Nawaf fullname: Nawaf, Cayce B. organization: Department of Urology, Yale School of Medicine, New Haven, CT 06511 – sequence: 8 givenname: Jaehyuk surname: Choi fullname: Choi, Jaehyuk organization: Department of Dermatology, Yale School of Medicine, New Haven, CT 06511 – sequence: 9 givenname: Arie S. surname: Belldegrun fullname: Belldegrun, Arie S. organization: Department of Urology, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095 – sequence: 10 givenname: Allan J. surname: Pantuck fullname: Pantuck, Allan J. organization: Department of Urology, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095 – sequence: 11 givenname: Harriet M. surname: Kluger fullname: Kluger, Harriet M. organization: Department of Medicine, Division of Oncology, Yale School of Medicine, New Haven, CT 06511 – sequence: 12 givenname: Kaya surname: Bilgüvar fullname: Bilgüvar, Kaya organization: Department of Genetics, Yale School of Medicine, New Haven, CT 06511 – sequence: 13 givenname: Richard P. surname: Lifton fullname: Lifton, Richard P. organization: Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06511 – sequence: 14 givenname: Brian surname: Shuch fullname: Shuch, Brian organization: Department of Pathology, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095 |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26864202$$D View this record in MEDLINE/PubMed |
| BookMark | eNqNks1rFTEUxYNU7Gt17UoZcONm2ptkksxsBClahYIbXbgKdzKJzWMmeSbzCvrXm3H6ai0IrhK4v3M49-OEHIUYLCHPKZxRUPx8FzCfUcGE4oJS_ohsKHS0lk0HR2QDwFTdNqw5Jic5bwGgEy08IcdMtrJhwDbk66UNcfKmMteY0Mw2-Z84-xiq6KqMycQJ5-iHak4YsotpWqs-VGa0mCpjx7FKNuC4fk3R-GKJT8ljh2O2z27fU_Ll_bvPFx_qq0-XHy_eXtVGSDHXVoHpmFKIAl0v5OAcV4651gFniMha0TPZIw5ogffOKAlOoqCStWqwnJ-SN6vvbt9PdjA2lKij3iU_YfqhI3r9dyX4a_0t3uhGKdnIxeD1rUGK3_c2z3ryeekFg437rKlqQQATXPwHKlsqRcdoQV89QLdxn8qYFkqxRvCypEK9vB_-LvVhQQUQK2BSzDlZp42ff6-g9OJHTUEvh6CXQ9B_DqHozh_oDtb_VhyiLIU7mnLdakYVFODFCmzzHNO9qI1UbRnPL3Ydyt4 |
| CitedBy_id | crossref_primary_10_1053_j_semdp_2021_09_004 crossref_primary_10_1177_24684570241302546 crossref_primary_10_3389_fonc_2023_1239405 crossref_primary_10_1016_j_celrep_2019_04_048 crossref_primary_10_1038_s41585_022_00676_0 crossref_primary_10_1016_j_euf_2016_06_015 crossref_primary_10_1038_s41598_021_83271_4 crossref_primary_10_1016_j_clgc_2017_05_018 crossref_primary_10_1097_MOU_0000000000000307 crossref_primary_10_1158_1078_0432_CCR_20_3506 crossref_primary_10_3389_fonc_2020_591001 crossref_primary_10_1038_nrdp_2017_9 crossref_primary_10_1038_s41581_020_0301_x crossref_primary_10_1097_RCT_0000000000001638 crossref_primary_10_1038_s41467_021_21068_9 crossref_primary_10_1016_j_critrevonc_2017_09_011 crossref_primary_10_1038_s41585_020_00382_9 crossref_primary_10_1016_j_cancergen_2016_07_002 crossref_primary_10_3390_cancers12010099 crossref_primary_10_1016_j_ctarc_2020_100172 crossref_primary_10_1111_cas_15170 crossref_primary_10_3389_fonc_2024_1477951 crossref_primary_10_1093_annonc_mdw689 crossref_primary_10_1007_s11864_018_0521_5 crossref_primary_10_1111_iju_14302 crossref_primary_10_1186_s12885_020_06733_4 crossref_primary_10_1016_j_urolonc_2017_12_012 crossref_primary_10_1016_j_yexmp_2020_104431 crossref_primary_10_1007_s00432_025_06146_5 crossref_primary_10_1111_pin_12704 crossref_primary_10_3390_medicines7080044 crossref_primary_10_1158_2159_8290_CD_17_0375 crossref_primary_10_1007_s00345_018_2355_y crossref_primary_10_1038_s44276_025_00128_3 crossref_primary_10_1002_cncr_30937 crossref_primary_10_1097_MOU_0000000000000516 crossref_primary_10_1097_PAP_0000000000000185 crossref_primary_10_1186_s40644_023_00535_0 crossref_primary_10_3346_jkms_2020_35_e31 crossref_primary_10_1097_PAS_0000000000000787 crossref_primary_10_3389_fonc_2020_627025 crossref_primary_10_1002_mc_22699 crossref_primary_10_1007_s00432_016_2304_3 crossref_primary_10_12998_wjcc_v12_i28_6230 crossref_primary_10_1053_j_semdp_2017_11_010 crossref_primary_10_1186_s12882_018_0884_7 crossref_primary_10_3390_ijms24020902 crossref_primary_10_1016_j_cell_2016_07_005 crossref_primary_10_1016_j_humpath_2022_07_022 crossref_primary_10_1038_s41581_020_00359_2 crossref_primary_10_1007_s00432_020_03236_4 crossref_primary_10_3389_fsurg_2021_763271 crossref_primary_10_1002_mgg3_1853 crossref_primary_10_1200_JCO_2018_79_2531 crossref_primary_10_1080_2162402X_2019_1606639 crossref_primary_10_1093_annonc_mdw676 crossref_primary_10_1186_s12957_020_01902_y crossref_primary_10_1016_j_humpath_2019_02_004 crossref_primary_10_3390_cancers12030729 crossref_primary_10_1038_s41467_022_28566_4 crossref_primary_10_1002_path_5022 crossref_primary_10_1097_PAS_0000000000002233 crossref_primary_10_1038_modpathol_2016_133 crossref_primary_10_1158_1078_0432_CCR_17_1057 crossref_primary_10_1186_s12864_017_3906_0 crossref_primary_10_1038_nrneph_2016_133 crossref_primary_10_1158_2159_8290_CD_18_0957 crossref_primary_10_1007_s00404_021_06094_8 crossref_primary_10_1177_03008916221077142 crossref_primary_10_1136_jclinpath_2016_203866 crossref_primary_10_1007_s00428_020_02839_z crossref_primary_10_3390_ijms22126237 crossref_primary_10_1002_gcc_22537 crossref_primary_10_1016_j_celrep_2021_110055 crossref_primary_10_1016_j_jtho_2017_03_005 crossref_primary_10_1016_j_juro_2017_04_116 crossref_primary_10_1016_j_urolonc_2018_10_027 crossref_primary_10_3389_fsurg_2022_922150 crossref_primary_10_15252_emmm_202013631 crossref_primary_10_1007_s10637_019_00817_0 crossref_primary_10_1016_j_clgc_2017_03_004 crossref_primary_10_1038_s41585_023_00847_7 crossref_primary_10_1016_j_ajoms_2023_11_002 crossref_primary_10_1111_bju_15084 crossref_primary_10_3389_fonc_2020_592501 crossref_primary_10_1016_j_celrep_2024_114350 crossref_primary_10_1016_j_ctarc_2022_100640 crossref_primary_10_1016_j_cllc_2018_12_013 crossref_primary_10_3389_fonc_2023_941835 crossref_primary_10_3390_cancers14174303 crossref_primary_10_3390_cancers11030422 crossref_primary_10_1016_j_euros_2024_10_002 crossref_primary_10_1016_j_ctrv_2022_102374 crossref_primary_10_1038_s41598_020_57534_5 |
| Cites_doi | 10.1016/j.ccr.2008.10.016 10.1038/modpathol.2013.96 10.1158/1078-0432.CCR-10-0821 10.1126/science.aaa1348 10.1056/NEJMoa1500596 10.1097/PAS.0b013e318299f0fb 10.1038/nm.3799 10.1016/j.urolonc.2014.11.021 10.1038/nbt.2514 10.1002/cncr.21288 10.1002/cncr.20541 10.1038/nature12634 10.1038/ng.2538 10.1038/cdd.2010.94 10.1097/00000478-200103000-00001 10.3892/ijo.2012.1669 10.2174/1389450114666140106101412 10.1038/nature12477 10.1200/JCO.2008.18.0000 10.1158/1078-0432.CCR-07-4921 10.1038/sj.bjc.6605298 10.1073/pnas.1222577110 10.4161/cc.24305 10.1073/pnas.91.21.9700 10.1158/2326-6066.CIR-15-0150 10.1038/nature12222 10.1016/j.abb.2011.12.019 10.1038/nature11632 10.1158/2159-8290.CD-12-0095 10.1056/NEJMoa1113205 10.1002/jso.1082 10.1038/ng.2323 10.1093/annonc/mdt578 10.1002/1097-0142(19930401)71:7<2292::AID-CNCR2820710720>3.0.CO;2-3 10.1111/bju.12781 10.1016/S1470-2045(12)70584-3 10.1371/journal.pone.0109924 10.1016/j.prp.2013.12.005 10.1136/jclinpath-2011-200216 10.1002/1097-0142(196809)22:3<556::AID-CNCR2820220310>3.0.CO;2-N 10.1038/ng0594-85 10.1016/j.eururo.2014.04.029 10.1038/ng.2891 10.1097/00000478-200404000-00002 10.1002/jcb.21340 10.1038/srep08829 10.1093/emboj/cdf521 10.1080/003130299104945 10.1038/ng.2956 10.1038/ncb2173 10.1111/j.1464-410X.2011.10785.x 10.1038/ncomms5988 10.1002/cncr.24768 10.1016/j.ccr.2014.07.014 10.1158/0008-5472.CAN-11-1562 10.1093/bioinformatics/btp324 10.1634/theoncologist.2011-0227 10.3389/fonc.2013.00203 10.1016/j.juro.2009.07.049 10.1038/ng.2699 |
| ContentType | Journal Article |
| Copyright | Volumes 1–89 and 106–113, copyright as a collective work only; author(s) retains copyright to individual articles Copyright National Academy of Sciences Feb 23, 2016 |
| Copyright_xml | – notice: Volumes 1–89 and 106–113, copyright as a collective work only; author(s) retains copyright to individual articles – notice: Copyright National Academy of Sciences Feb 23, 2016 |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QG 7QL 7QP 7QR 7SN 7SS 7T5 7TK 7TM 7TO 7U9 8FD C1K FR3 H94 M7N P64 RC3 7X8 5PM |
| DOI | 10.1073/pnas.1525735113 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Animal Behavior Abstracts Bacteriology Abstracts (Microbiology B) Calcium & Calcified Tissue Abstracts Chemoreception Abstracts Ecology Abstracts Entomology Abstracts (Full archive) Immunology Abstracts Neurosciences Abstracts Nucleic Acids Abstracts Oncogenes and Growth Factors Abstracts Virology and AIDS Abstracts Technology Research Database Environmental Sciences and Pollution Management Engineering Research Database AIDS and Cancer Research Abstracts Algology Mycology and Protozoology Abstracts (Microbiology C) Biotechnology and BioEngineering Abstracts Genetics Abstracts MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Virology and AIDS Abstracts Oncogenes and Growth Factors Abstracts Technology Research Database Nucleic Acids Abstracts Ecology Abstracts Neurosciences Abstracts Biotechnology and BioEngineering Abstracts Environmental Sciences and Pollution Management Entomology Abstracts Genetics Abstracts Animal Behavior Abstracts Bacteriology Abstracts (Microbiology B) Algology Mycology and Protozoology Abstracts (Microbiology C) AIDS and Cancer Research Abstracts Chemoreception Abstracts Immunology Abstracts Engineering Research Database Calcium & Calcified Tissue Abstracts MEDLINE - Academic |
| DatabaseTitleList | CrossRef MEDLINE - Academic Genetics Abstracts MEDLINE Virology and AIDS Abstracts |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Sciences (General) |
| DocumentTitleAlternate | Sarcomatoid transformation in clear cell RCC |
| EISSN | 1091-6490 |
| EndPage | 2175 |
| ExternalDocumentID | PMC4776463 3982512351 26864202 10_1073_pnas_1525735113 113_8_2170 26467825 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural Feature |
| GrantInformation_xml | – fundername: NCI NIH HHS grantid: K24 CA172123 – fundername: Howard Hughes Medical Institute – fundername: NIDDK NIH HHS grantid: P30 DK079310 – fundername: NCATS NIH HHS grantid: KL2 TR000140 – fundername: NCI NIH HHS grantid: P30 CA016042 – fundername: NCI NIH HHS grantid: K08-CA191019 – fundername: NCI NIH HHS grantid: K08 CA191019 – fundername: Howard Hughes Medical Institute (HHMI) – fundername: HHS | NIH | National Cancer Institute (NCI) grantid: K08-CA191019 – fundername: HHS | NIH | National Cancer Institute (NCI) grantid: KL2 TR000140 |
| GroupedDBID | --- -DZ -~X .55 0R~ 123 29P 2AX 2FS 2WC 4.4 53G 5RE 5VS 85S AACGO AAFWJ AANCE ABBHK ABOCM ABPLY ABPPZ ABTLG ABXSQ ABZEH ACGOD ACHIC ACIWK ACNCT ACPRK ADQXQ ADULT AENEX AEUPB AEXZC AFFNX AFRAH ALMA_UNASSIGNED_HOLDINGS AQVQM BKOMP CS3 D0L DCCCD DIK DU5 E3Z EBS EJD F5P FRP GX1 H13 HH5 HYE IPSME JAAYA JBMMH JENOY JHFFW JKQEH JLS JLXEF JPM JSG JST KQ8 L7B LU7 N9A N~3 O9- OK1 PNE PQQKQ R.V RHI RNA RNS RPM RXW SA0 SJN TAE TN5 UKR W8F WH7 WOQ WOW X7M XSW Y6R YBH YKV YSK ZCA ~02 ~KM - 02 0R 1AW 55 AAPBV ABFLS ABPTK ADACO ADZLD ASUFR DNJUQ DOOOF DWIUU DZ F20 JSODD KM PQEST RHF VQA X XHC ZA5 AAYXX AFOSN CITATION CGR CUY CVF ECM EIF NPM 7QG 7QL 7QP 7QR 7SN 7SS 7T5 7TK 7TM 7TO 7U9 8FD C1K FR3 H94 M7N P64 RC3 7X8 5PM |
| ID | FETCH-LOGICAL-c565t-e70c9277aa5afb56dff37f2f8f032aaa285b26baadae03bfc760f6a516287de33 |
| ISSN | 0027-8424 1091-6490 |
| IngestDate | Thu Aug 21 18:16:15 EDT 2025 Thu Jul 10 20:13:54 EDT 2025 Fri Jul 11 07:01:47 EDT 2025 Mon Jun 30 07:41:39 EDT 2025 Thu Apr 03 07:09:46 EDT 2025 Tue Jul 01 01:53:40 EDT 2025 Thu Apr 24 23:08:24 EDT 2025 Wed Nov 11 00:29:25 EST 2020 Sun Aug 24 12:10:52 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 8 |
| Keywords | kidney cancer dedifferentiation transformation sarcomatoid p53 |
| Language | English |
| License | Freely available online through the PNAS open access option. |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c565t-e70c9277aa5afb56dff37f2f8f032aaa285b26baadae03bfc760f6a516287de33 |
| Notes | SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 Author contributions: R.P.L. and B.S. designed research; M.J.M., A.J.A., Z.X., C.B.N., K.B., R.P.L., and B.S. performed research; J.W.S., J.C., A.S.B., A.J.P., H.M.K., and B.S. contributed new reagents/analytic tools; M.B., S.Z., J.W.S., Z.X., J.C., R.P.L., and B.S. analyzed data; and M.B., R.P.L., and B.S. wrote the paper. Reviewers: J.B., University of Texas Southwestern Medical Center; and D.A.H., Massachusetts General Hospital. Contributed by Richard P. Lifton, December 31, 2015 (sent for review December 18, 2015; reviewed by James Brugarolas and Daniel A. Haber) |
| OpenAccessLink | https://escholarship.org/content/qt4h49r436/qt4h49r436.pdf?t=ru0j73 |
| PMID | 26864202 |
| PQID | 1772453649 |
| PQPubID | 42026 |
| PageCount | 6 |
| ParticipantIDs | proquest_journals_1772453649 pubmed_primary_26864202 crossref_citationtrail_10_1073_pnas_1525735113 pnas_primary_113_8_2170 jstor_primary_26467825 pubmedcentral_primary_oai_pubmedcentral_nih_gov_4776463 proquest_miscellaneous_1780502535 crossref_primary_10_1073_pnas_1525735113 proquest_miscellaneous_1768165921 |
| ProviderPackageCode | RNA PNE CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2016-02-23 |
| PublicationDateYYYYMMDD | 2016-02-23 |
| PublicationDate_xml | – month: 02 year: 2016 text: 2016-02-23 day: 23 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Washington |
| PublicationTitle | Proceedings of the National Academy of Sciences - PNAS |
| PublicationTitleAlternate | Proc Natl Acad Sci U S A |
| PublicationYear | 2016 |
| Publisher | National Academy of Sciences National Acad Sciences |
| Publisher_xml | – name: National Academy of Sciences – name: National Acad Sciences |
| References | Davis CF (e_1_3_4_32_2) 2014; 26 Katoh M (e_1_3_4_52_2) 2012; 41 Goh G (e_1_3_4_22_2) 2014; 46 Guan B (e_1_3_4_33_2) 2011; 71 Gnarra JR (e_1_3_4_45_2) 1994; 7 Oda H (e_1_3_4_36_2) 1995; 55 Shuch B (e_1_3_4_20_2) 2010; 116 Pritchard CC (e_1_3_4_31_2) 2014; 5 Delahunt B (e_1_3_4_6_2) 2013; 37 Herman JG (e_1_3_4_46_2) 1994; 91 Furukawa T (e_1_3_4_50_2) 2015; 5 Conant JL (e_1_3_4_21_2) 2011; 64 Bitler BG (e_1_3_4_59_2) 2015; 21 Gordan JD (e_1_3_4_49_2) 2008; 14 Li HJ (e_1_3_4_57_2) 2007; 102 Gerlinger M (e_1_3_4_44_2) 2012; 366 Chang CJ (e_1_3_4_37_2) 2011; 13 Patard JJ (e_1_3_4_48_2) 2009; 101 Shuch B (e_1_3_4_4_2) 2012; 109 Nanus DM (e_1_3_4_12_2) 2004; 101 Peña-Llopis S (e_1_3_4_41_2) 2012; 44 Hong B (e_1_3_4_58_2) 2014; 15 Shuch B (e_1_3_4_1_2) 2009; 182 Delahunt B (e_1_3_4_16_2) 1999; 31 Zhao S (e_1_3_4_25_2) 2013; 110 e_1_3_4_11_2 e_1_3_4_13_2 Shuch B (e_1_3_4_3_2) 2015; 67 Martin SA (e_1_3_4_60_2) 2010; 16 Kapur P (e_1_3_4_42_2) 2013; 14 Rizvi NA (e_1_3_4_61_2) 2015; 348 Golshayan AR (e_1_3_4_10_2) 2009; 27 Kuroiwa K (e_1_3_4_19_2) 2001; 77 Oda H (e_1_3_4_18_2) 1993; 71 Li H (e_1_3_4_23_2) 2009; 25 Alexandrov LB (e_1_3_4_30_2) 2013; 500 Bosse T (e_1_3_4_34_2) 2013; 26 Joseph RW (e_1_3_4_63_2) 2015; 3 Cibulskis K (e_1_3_4_24_2) 2013; 31 Le DT (e_1_3_4_62_2) 2015; 372 Cerami E (e_1_3_4_29_2) 2012; 2 Maschietto M (e_1_3_4_40_2) 2014; 9 Merrill MM (e_1_3_4_8_2) 2015; 33 Sato Y (e_1_3_4_35_2) 2013; 45 Bardeesy N (e_1_3_4_39_2) 1995; 55 Cheville JC (e_1_3_4_7_2) 2004; 28 Anani W (e_1_3_4_14_2) 2014; 210 Cancer Genome Atlas Research Network (e_1_3_4_28_2) 2013; 499 Darai-Ramqvist E (e_1_3_4_15_2) 2013; 3 e_1_3_4_47_2 Hiroi N (e_1_3_4_56_2) 2002; 21 Peradziryi H (e_1_3_4_55_2) 2012; 524 Zhang BY (e_1_3_4_5_2) 2015; 115 Kogan-Sakin I (e_1_3_4_38_2) 2011; 18 Gerlinger M (e_1_3_4_43_2) 2014; 46 Morris LG (e_1_3_4_53_2) 2013; 45 Shuch B (e_1_3_4_9_2) 2012; 17 de Peralta-Venturina M (e_1_3_4_2_2) 2001; 25 Jones TD (e_1_3_4_17_2) 2005; 104 Feng GH (e_1_3_4_54_2) 2000; 60 Kandoth C (e_1_3_4_27_2) 2013; 502 Morris LG (e_1_3_4_51_2) 2013; 12 Abecasis GR (e_1_3_4_26_2) 2012; 491 |
| References_xml | – volume: 14 start-page: 435 year: 2008 ident: e_1_3_4_49_2 article-title: HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma publication-title: Cancer Cell doi: 10.1016/j.ccr.2008.10.016 – volume: 26 start-page: 1525 year: 2013 ident: e_1_3_4_34_2 article-title: Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations, TP53 and microsatellite instability in endometrial cancer publication-title: Mod Pathol doi: 10.1038/modpathol.2013.96 – volume: 16 start-page: 5107 year: 2010 ident: e_1_3_4_60_2 article-title: Therapeutic targeting of the DNA mismatch repair pathway publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-10-0821 – volume: 348 start-page: 124 year: 2015 ident: e_1_3_4_61_2 article-title: Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer publication-title: Science doi: 10.1126/science.aaa1348 – volume: 372 start-page: 2509 year: 2015 ident: e_1_3_4_62_2 article-title: PD-1 blockade in tumors with mismatch-repair deficiency publication-title: N Engl J Med doi: 10.1056/NEJMoa1500596 – volume: 37 start-page: 1490 year: 2013 ident: e_1_3_4_6_2 article-title: The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters publication-title: Am J Surg Pathol doi: 10.1097/PAS.0b013e318299f0fb – volume: 21 start-page: 231 year: 2015 ident: e_1_3_4_59_2 article-title: Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers publication-title: Nat Med doi: 10.1038/nm.3799 – volume: 33 start-page: 166.e21 year: 2015 ident: e_1_3_4_8_2 article-title: Clinically nonmetastatic renal cell carcinoma with sarcomatoid dedifferentiation: Natural history and outcomes after surgical resection with curative intent publication-title: Urol Oncol doi: 10.1016/j.urolonc.2014.11.021 – volume: 31 start-page: 213 year: 2013 ident: e_1_3_4_24_2 article-title: Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples publication-title: Nat Biotechnol doi: 10.1038/nbt.2514 – volume: 104 start-page: 1195 year: 2005 ident: e_1_3_4_17_2 article-title: Clonal divergence and genetic heterogeneity in clear cell renal cell carcinomas with sarcomatoid transformation publication-title: Cancer doi: 10.1002/cncr.21288 – volume: 55 start-page: 658 year: 1995 ident: e_1_3_4_36_2 article-title: Mutations of the p53 gene and p53 protein overexpression are associated with sarcomatoid transformation in renal cell carcinomas publication-title: Cancer Res – volume: 101 start-page: 1545 year: 2004 ident: e_1_3_4_12_2 article-title: Active chemotherapy for sarcomatoid and rapidly progressing renal cell carcinoma publication-title: Cancer doi: 10.1002/cncr.20541 – volume: 502 start-page: 333 year: 2013 ident: e_1_3_4_27_2 article-title: Mutational landscape and significance across 12 major cancer types publication-title: Nature doi: 10.1038/nature12634 – volume: 45 start-page: 253 year: 2013 ident: e_1_3_4_53_2 article-title: Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation publication-title: Nat Genet doi: 10.1038/ng.2538 – volume: 55 start-page: 215 year: 1995 ident: e_1_3_4_39_2 article-title: Clonal expansion and attenuated apoptosis in Wilms’ tumors are associated with p53 gene mutations publication-title: Cancer Res – volume: 18 start-page: 271 year: 2011 ident: e_1_3_4_38_2 article-title: Mutant p53(R175H) upregulates Twist1 expression and promotes epithelial-mesenchymal transition in immortalized prostate cells publication-title: Cell Death Differ doi: 10.1038/cdd.2010.94 – volume: 25 start-page: 275 year: 2001 ident: e_1_3_4_2_2 article-title: Sarcomatoid differentiation in renal cell carcinoma: A study of 101 cases publication-title: Am J Surg Pathol doi: 10.1097/00000478-200103000-00001 – volume: 41 start-page: 1913 year: 2012 ident: e_1_3_4_52_2 article-title: Function and cancer genomics of FAT family genes (review) publication-title: Int J Oncol doi: 10.3892/ijo.2012.1669 – volume: 15 start-page: 80 year: 2014 ident: e_1_3_4_58_2 article-title: Targeting tumor suppressor p53 for cancer therapy: Strategies, challenges and opportunities publication-title: Curr Drug Targets doi: 10.2174/1389450114666140106101412 – volume: 500 start-page: 415 year: 2013 ident: e_1_3_4_30_2 article-title: Signatures of mutational processes in human cancer publication-title: Nature doi: 10.1038/nature12477 – volume: 27 start-page: 235 year: 2009 ident: e_1_3_4_10_2 article-title: Metastatic sarcomatoid renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy publication-title: J Clin Oncol doi: 10.1200/JCO.2008.18.0000 – ident: e_1_3_4_47_2 doi: 10.1158/1078-0432.CCR-07-4921 – volume: 101 start-page: 1417 year: 2009 ident: e_1_3_4_48_2 article-title: Absence of VHL gene alteration and high VEGF expression are associated with tumour aggressiveness and poor survival of renal-cell carcinoma publication-title: Br J Cancer doi: 10.1038/sj.bjc.6605298 – volume: 110 start-page: 2916 year: 2013 ident: e_1_3_4_25_2 article-title: Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma publication-title: Proc Natl Acad Sci USA doi: 10.1073/pnas.1222577110 – volume: 12 start-page: 1011 year: 2013 ident: e_1_3_4_51_2 article-title: The FAT epidemic: A gene family frequently mutated across multiple human cancer types publication-title: Cell Cycle doi: 10.4161/cc.24305 – volume: 91 start-page: 9700 year: 1994 ident: e_1_3_4_46_2 article-title: Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma publication-title: Proc Natl Acad Sci USA doi: 10.1073/pnas.91.21.9700 – volume: 3 start-page: 1303 year: 2015 ident: e_1_3_4_63_2 article-title: PD-1 and PD-L1 expression in renal cell carcinoma with sarcomatoid differentiation publication-title: Cancer Immunol Res doi: 10.1158/2326-6066.CIR-15-0150 – volume: 499 start-page: 43 year: 2013 ident: e_1_3_4_28_2 article-title: Comprehensive molecular characterization of clear cell renal cell carcinoma publication-title: Nature doi: 10.1038/nature12222 – volume: 524 start-page: 71 year: 2012 ident: e_1_3_4_55_2 article-title: The many roles of PTK7: A versatile regulator of cell-cell communication publication-title: Arch Biochem Biophys doi: 10.1016/j.abb.2011.12.019 – volume: 60 start-page: 1736 year: 2000 ident: e_1_3_4_54_2 article-title: TSG101 protein steady-state level is regulated posttranslationally by an evolutionarily conserved COOH-terminal sequence publication-title: Cancer Res – volume: 491 start-page: 56 year: 2012 ident: e_1_3_4_26_2 article-title: An integrated map of genetic variation from 1,092 human genomes publication-title: Nature doi: 10.1038/nature11632 – volume: 2 start-page: 401 year: 2012 ident: e_1_3_4_29_2 article-title: The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-12-0095 – volume: 366 start-page: 883 year: 2012 ident: e_1_3_4_44_2 article-title: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing publication-title: N Engl J Med doi: 10.1056/NEJMoa1113205 – volume: 77 start-page: 123 year: 2001 ident: e_1_3_4_19_2 article-title: Cell proliferative activity and expression of cell-cell adhesion factors (E-cadherin, alpha-, beta-, and gamma-catenin, and p120) in sarcomatoid renal cell carcinoma publication-title: J Surg Oncol doi: 10.1002/jso.1082 – volume: 44 start-page: 751 year: 2012 ident: e_1_3_4_41_2 article-title: BAP1 loss defines a new class of renal cell carcinoma publication-title: Nat Genet doi: 10.1038/ng.2323 – ident: e_1_3_4_11_2 doi: 10.1093/annonc/mdt578 – volume: 71 start-page: 2292 year: 1993 ident: e_1_3_4_18_2 article-title: Sarcomatoid renal cell carcinoma. A study of its proliferative activity publication-title: Cancer doi: 10.1002/1097-0142(19930401)71:7<2292::AID-CNCR2820710720>3.0.CO;2-3 – volume: 115 start-page: 405 year: 2015 ident: e_1_3_4_5_2 article-title: A novel prognostic model for patients with sarcomatoid renal cell carcinoma publication-title: BJU Int doi: 10.1111/bju.12781 – volume: 14 start-page: 159 year: 2013 ident: e_1_3_4_42_2 article-title: Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: A retrospective analysis with independent validation publication-title: Lancet Oncol doi: 10.1016/S1470-2045(12)70584-3 – volume: 9 start-page: e109924 year: 2014 ident: e_1_3_4_40_2 article-title: TP53 mutational status is a potential marker for risk stratification in Wilms tumour with diffuse anaplasia publication-title: PLoS One doi: 10.1371/journal.pone.0109924 – volume: 210 start-page: 217 year: 2014 ident: e_1_3_4_14_2 article-title: A series of collision tumors in the genitourinary tract with a review of the literature publication-title: Pathol Res Pract doi: 10.1016/j.prp.2013.12.005 – volume: 64 start-page: 1088 year: 2011 ident: e_1_3_4_21_2 article-title: Sarcomatoid renal cell carcinoma is an example of epithelial--mesenchymal transition publication-title: J Clin Pathol doi: 10.1136/jclinpath-2011-200216 – ident: e_1_3_4_13_2 doi: 10.1002/1097-0142(196809)22:3<556::AID-CNCR2820220310>3.0.CO;2-N – volume: 7 start-page: 85 year: 1994 ident: e_1_3_4_45_2 article-title: Mutations of the VHL tumour suppressor gene in renal carcinoma publication-title: Nat Genet doi: 10.1038/ng0594-85 – volume: 67 start-page: 85 year: 2015 ident: e_1_3_4_3_2 article-title: Understanding pathologic variants of renal cell carcinoma: Distilling therapeutic opportunities from biologic complexity publication-title: Eur Urol doi: 10.1016/j.eururo.2014.04.029 – volume: 46 start-page: 225 year: 2014 ident: e_1_3_4_43_2 article-title: Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing publication-title: Nat Genet doi: 10.1038/ng.2891 – volume: 28 start-page: 435 year: 2004 ident: e_1_3_4_7_2 article-title: Sarcomatoid renal cell carcinoma: An examination of underlying histologic subtype and an analysis of associations with patient outcome publication-title: Am J Surg Pathol doi: 10.1097/00000478-200404000-00002 – volume: 102 start-page: 1021 year: 2007 ident: e_1_3_4_57_2 article-title: RIF-1, a novel nuclear receptor corepressor that associates with the nuclear matrix publication-title: J Cell Biochem doi: 10.1002/jcb.21340 – volume: 5 start-page: 8829 year: 2015 ident: e_1_3_4_50_2 article-title: Whole exome sequencing reveals recurrent mutations in BRCA2 and FAT genes in acinar cell carcinomas of the pancreas publication-title: Sci Rep doi: 10.1038/srep08829 – volume: 21 start-page: 5235 year: 2002 ident: e_1_3_4_56_2 article-title: Mammalian Rcd1 is a novel transcriptional cofactor that mediates retinoic acid-induced cell differentiation publication-title: EMBO J doi: 10.1093/emboj/cdf521 – volume: 31 start-page: 185 year: 1999 ident: e_1_3_4_16_2 article-title: Sarcomatoid renal carcinoma: The final common dedifferentiation pathway of renal epithelial malignancies publication-title: Pathology doi: 10.1080/003130299104945 – volume: 46 start-page: 613 year: 2014 ident: e_1_3_4_22_2 article-title: Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors publication-title: Nat Genet doi: 10.1038/ng.2956 – volume: 13 start-page: 317 year: 2011 ident: e_1_3_4_37_2 article-title: p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs publication-title: Nat Cell Biol doi: 10.1038/ncb2173 – volume: 109 start-page: 1600 year: 2012 ident: e_1_3_4_4_2 article-title: Impact of pathological tumour characteristics in patients with sarcomatoid renal cell carcinoma publication-title: BJU Int doi: 10.1111/j.1464-410X.2011.10785.x – volume: 5 start-page: 4988 year: 2014 ident: e_1_3_4_31_2 article-title: Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer publication-title: Nat Commun doi: 10.1038/ncomms5988 – volume: 116 start-page: 616 year: 2010 ident: e_1_3_4_20_2 article-title: Histologic evaluation of metastases in renal cell carcinoma with sarcomatoid transformation and its implications for systemic therapy publication-title: Cancer doi: 10.1002/cncr.24768 – volume: 26 start-page: 319 year: 2014 ident: e_1_3_4_32_2 article-title: The somatic genomic landscape of chromophobe renal cell carcinoma publication-title: Cancer Cell doi: 10.1016/j.ccr.2014.07.014 – volume: 71 start-page: 6718 year: 2011 ident: e_1_3_4_33_2 article-title: ARID1A, a factor that promotes formation of SWI/SNF-mediated chromatin remodeling, is a tumor suppressor in gynecologic cancers publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-11-1562 – volume: 25 start-page: 1754 year: 2009 ident: e_1_3_4_23_2 article-title: Fast and accurate short read alignment with Burrows-Wheeler transform publication-title: Bioinformatics doi: 10.1093/bioinformatics/btp324 – volume: 17 start-page: 46 year: 2012 ident: e_1_3_4_9_2 article-title: Sarcomatoid renal cell carcinoma: A comprehensive review of the biology and current treatment strategies publication-title: Oncologist doi: 10.1634/theoncologist.2011-0227 – volume: 3 start-page: 203 year: 2013 ident: e_1_3_4_15_2 article-title: Microenvironment-dependent phenotypic changes in a SCID mouse model for malignant mesothelioma publication-title: Front Oncol doi: 10.3389/fonc.2013.00203 – volume: 182 start-page: 2164 year: 2009 ident: e_1_3_4_1_2 article-title: Cytoreductive nephrectomy for kidney cancer with sarcomatoid histology--is up-front resection indicated and, if not, is it avoidable? publication-title: J Urol doi: 10.1016/j.juro.2009.07.049 – volume: 45 start-page: 860 year: 2013 ident: e_1_3_4_35_2 article-title: Integrated molecular analysis of clear-cell renal cell carcinoma publication-title: Nat Genet doi: 10.1038/ng.2699 |
| SSID | ssj0009580 |
| Score | 2.510385 |
| Snippet | The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome... Parts of clear cell renal cell carcinomas (ccRCCs) sometimes have histologic features characteristic of a sarcoma. So-called sarcomatoid tumors are more... |
| SourceID | pubmedcentral proquest pubmed crossref pnas jstor |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 2170 |
| SubjectTerms | Aged Biological Sciences Carcinoma, Renal Cell - classification Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - pathology Cell Dedifferentiation - genetics Chromosomes DNA Mismatch Repair - genetics Exome Female Genes Genes, p53 Genomics Humans Kidney cancer Kidney Neoplasms - classification Kidney Neoplasms - genetics Kidney Neoplasms - pathology Loss of Heterozygosity Male Middle Aged Mutation Nuclear Proteins - genetics Oncogenes Polymorphism, Single Nucleotide Prognosis Transcription Factors - genetics Tumor Suppressor Proteins - genetics Tumors Ubiquitin Thiolesterase - genetics |
| Title | Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma |
| URI | https://www.jstor.org/stable/26467825 http://www.pnas.org/content/113/8/2170.abstract https://www.ncbi.nlm.nih.gov/pubmed/26864202 https://www.proquest.com/docview/1772453649 https://www.proquest.com/docview/1768165921 https://www.proquest.com/docview/1780502535 https://pubmed.ncbi.nlm.nih.gov/PMC4776463 |
| Volume | 113 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3Nb9MwFLfKuHBBDBgEBgoSh6EoJbETxzlOCDZNoprEJgqXyHHsLRJK0Npe9v_wf_L8ETetOgRcIjd5sRy_n997dt8HQm-xVIUAkRjLguVxJrCKGackhrVVFhgnvC51NPLnGT29zM7m-Xwy-TXyWlot66m43RlX8j9chXvAVx0l-w-c9Z3CDWgDf-EKHIbrX_H4RJqgYh2967Iu33oLcAEI7sEc7dtG14Hw1ql1bRS6WkSkT-2jG6kNUtMUurAQdMnHJuu5V3GLwaFgNpwgHq_jUZyQWERxdD4bVTdutyOCvl9zczz7RdcTu_InPLxtxqf50depx4KOUOxdNy2Pzqbjo4rUeDfbaOJxpu-dgxvLaAx6M7OR1VNpxTJYNTHNbGFRL7dtEKsDKNuQwrYYidPo8DPfqS1AvOkSxx1fmDJQhf5TlawVo3dXBKMRdDrO76H7GHYjulDGyTwd5XZmNtLJDXzIIFWQ91t9bxg_1v9VJ9UFol0bnG0_3ZHhc_EIPXQ7lvDYwm8fTWT3GO0PMxoeucTl756gbw6P4TYew16FIzyGm3gM2y40eAw1CEODR9v0eHyKLj99vPhwGrvSHbGAHcISVn4iSpgrznOu6pw2SpFCYcVUQjDnHLO8xrTmvOEyIbUSBU0U5XlKYQffSEIO0F7Xd_I5CjEtmaCJ4IkE61mUNcsVK0vFGqZ4xuoATYc5rYTLa6_Lq_yojH9FQSo9v9WaCQE68i_8tCld7iY9MEzydAMSAvTMkPr3U1KxSuMuQIcDIysnKqBHQE2WE0BwgN74xyDI9WTyTvYrTUNZqp0c0j_RsCSHXQoxAzDYGA2N0QwnOEDFBmo8gU4kv_mka69NQvmsKOC7yIu7vvYlerBezodob3mzkq_AFl_Wr81K-A2_5ODV |
| linkProvider | Geneva Foundation for Medical Education and Research |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Genomic+characterization+of+sarcomatoid+transformation+in+clear+cell+renal+cell+carcinoma&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+-+PNAS&rft.au=Bi%2C+Mark&rft.au=Zhao%2C+Siming&rft.au=Said%2C+Jonathan+W.&rft.au=Merino%2C+Maria+J.&rft.date=2016-02-23&rft.pub=National+Academy+of+Sciences&rft.issn=0027-8424&rft.eissn=1091-6490&rft.volume=113&rft.issue=8&rft.spage=2170&rft.epage=2175&rft_id=info:doi/10.1073%2Fpnas.1525735113&rft.externalDocID=26467825 |
| thumbnail_m | http://utb.summon.serialssolutions.com/2.0.0/image/custom?url=http%3A%2F%2Fwww.pnas.org%2Fcontent%2F113%2F8.cover.gif |
| thumbnail_s | http://utb.summon.serialssolutions.com/2.0.0/image/custom?url=http%3A%2F%2Fwww.pnas.org%2Fcontent%2F113%2F8.cover.gif |