IDH2 Mutations Define a Unique Subtype of Breast Cancer with Altered Nuclear Polarity

Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted seq...

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Published inCancer research (Chicago, Ill.) Vol. 76; no. 24; pp. 7118 - 7129
Main Authors Chiang, Sarah, Weigelt, Britta, Wen, Huei-Chi, Pareja, Fresia, Raghavendra, Ashwini, Martelotto, Luciano G, Burke, Kathleen A, Basili, Thais, Li, Anqi, Geyer, Felipe C, Piscuoglio, Salvatore, Ng, Charlotte K Y, Jungbluth, Achim A, Balss, Jörg, Pusch, Stefan, Baker, Gabrielle M, Cole, Kimberly S, von Deimling, Andreas, Batten, Julie M, Marotti, Jonathan D, Soh, Hwei-Choo, McCalip, Benjamin L, Serrano, Jonathan, Lim, Raymond S, Siziopikou, Kalliopi P, Lu, Song, Liu, Xiaolong, Hammour, Tarek, Brogi, Edi, Snuderl, Matija, Iafrate, A John, Reis-Filho, Jorge S, Schnitt, Stuart J
Format Journal Article
LanguageEnglish
Published United States 15.12.2016
Subjects
Biomarkers, Tumor - genetics
Blotting, Western
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Carcinoma, Papillary - genetics
Carcinoma, Papillary - pathology
Class I Phosphatidylinositol 3-Kinases
DNA Mutational Analysis
Female
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
Isocitrate Dehydrogenase - genetics
Phosphatidylinositol 3-Kinases - genetics
Polymerase Chain Reaction
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Abstract Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1 One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R hotspot mutation. Functional studies demonstrated that IDH2 and PIK3CA hotspot mutations are likely drivers of SPCRP, resulting in its reversed nuclear polarization phenotype. Our results offer a molecular definition of SPCRP as a distinct breast cancer subtype. Concurrent IDH2 and PIK3CA mutations may help diagnose SPCRP and possibly direct effective treatment. Cancer Res; 76(24); 7118-29. ©2016 AACR.
AbstractList Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1 One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R hotspot mutation. Functional studies demonstrated that IDH2 and PIK3CA hotspot mutations are likely drivers of SPCRP, resulting in its reversed nuclear polarization phenotype. Our results offer a molecular definition of SPCRP as a distinct breast cancer subtype. Concurrent IDH2 and PIK3CA mutations may help diagnose SPCRP and possibly direct effective treatment. Cancer Res; 76(24); 7118-29. ©2016 AACR.
This study reports molecular biomarkers for a rare form of breast cancer by identifying IDH2 and PIK3CA driver mutations that may help diagnose this disease and possibly direct its more effective treatment. Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1. One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R hotspot mutation. Functional studies demonstrated that IDH2 and PIK3CA hotspot mutations are likely drivers of SPCRP, resulting in its reversed nuclear polarization phenotype. Our results offer a molecular definition of SPCRP as a distinct breast cancer subtype. Concurrent IDH2 and PIK3CA mutations may help diagnose SPCRP and possibly direct effective treatment. Cancer Res; 76(24); 7118-29. [copy2016 AACR.
Abstract Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1. One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R hotspot mutation. Functional studies demonstrated that IDH2 and PIK3CA hotspot mutations are likely drivers of SPCRP, resulting in its reversed nuclear polarization phenotype. Our results offer a molecular definition of SPCRP as a distinct breast cancer subtype. Concurrent IDH2 and PIK3CA mutations may help diagnose SPCRP and possibly direct effective treatment. Cancer Res; 76(24); 7118–29. ©2016 AACR.
Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2 , of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1 . One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R mutation. Functional studies demonstrated that IDH2 and PIK3CA hotspot mutations are likely drivers of SPCRP, resulting in its reversed nuclear polarization phenotype. Our results offer a molecular definition of SPCRP as a distinct breast cancer subtype. Concurrent IDH2 and PIK3CA mutations may help diagnose SPCRP and possibly direct effective treatment.
Author Brogi, Edi
Geyer, Felipe C
Lu, Song
Liu, Xiaolong
Weigelt, Britta
Li, Anqi
Iafrate, A John
Serrano, Jonathan
Jungbluth, Achim A
Hammour, Tarek
Martelotto, Luciano G
Pusch, Stefan
Balss, Jörg
Soh, Hwei-Choo
Snuderl, Matija
Marotti, Jonathan D
Baker, Gabrielle M
Ng, Charlotte K Y
Schnitt, Stuart J
Raghavendra, Ashwini
Burke, Kathleen A
Lim, Raymond S
Chiang, Sarah
Cole, Kimberly S
Pareja, Fresia
Wen, Huei-Chi
Batten, Julie M
von Deimling, Andreas
McCalip, Benjamin L
Siziopikou, Kalliopi P
Basili, Thais
Reis-Filho, Jorge S
Piscuoglio, Salvatore
AuthorAffiliation 14 Maine Medical Center, Portland, ME, USA
7 Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
4 Department of Pathology, University of Iowa Hospital and Clinics, Iowa City, IA, USA
1 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
13 ABQ Health Partners, Albuquerque, NM, USA
9 Miami Valley Hospital, Dayton, OH, USA
12 Department of Pathology, Mon General Hospital, Morgantown, WV, USA
5 Department of Neuropathology, Institute of Pathology, INF 224, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
6 Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
16 Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
10 Department of Pathology, New York University Langone Medical Center and Medical School, New York, NY, USA
15 Department of Pathology, Harvard Medical School, Boston, MA, USA
2 German Consortium of Translational Cancer Research (DKTK), Clinical Cooperation Unit Neuropathology, G
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/27913435$$D View this record in MEDLINE/PubMed
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Snippet Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its...
Abstract Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe...
This study reports molecular biomarkers for a rare form of breast cancer by identifying IDH2 and PIK3CA driver mutations that may help diagnose this disease...
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StartPage 7118
SubjectTerms Biomarkers, Tumor - genetics
Blotting, Western
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Carcinoma, Papillary - genetics
Carcinoma, Papillary - pathology
Class I Phosphatidylinositol 3-Kinases
DNA Mutational Analysis
Female
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
Isocitrate Dehydrogenase - genetics
Phosphatidylinositol 3-Kinases - genetics
Polymerase Chain Reaction
Title IDH2 Mutations Define a Unique Subtype of Breast Cancer with Altered Nuclear Polarity
URI https://www.ncbi.nlm.nih.gov/pubmed/27913435
https://search.proquest.com/docview/1845838662
https://search.proquest.com/docview/1868328326
https://pubmed.ncbi.nlm.nih.gov/PMC5502804
Volume 76
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