Identification of genomic alterations in pancreatic cancer using array-based comparative genomic hybridization

Genomic aberration is a common feature of human cancers and also is one of the basic mechanisms that lead to overexpression of oncogenes and underexpression of tumor suppressor genes. Our study aims to identify frequent genomic changes in pancreatic cancer. We used array comparative genomic hybridiz...

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Published inPloS one Vol. 9; no. 12; p. e114616
Main Authors Liang, Jian-Wei, Shi, Zhi-Zhou, Shen, Tian-Yun, Che, Xu, Wang, Zheng, Shi, Su-Sheng, Xu, Xin, Cai, Yan, Zhao, Ping, Wang, Cheng-Feng, Zhou, Zhi-Xiang, Wang, Ming-Rong
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 11.12.2014
Public Library of Science (PLoS)
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Summary:Genomic aberration is a common feature of human cancers and also is one of the basic mechanisms that lead to overexpression of oncogenes and underexpression of tumor suppressor genes. Our study aims to identify frequent genomic changes in pancreatic cancer. We used array comparative genomic hybridization (array CGH) to identify recurrent genomic alterations and validated the protein expression of selected genes by immunohistochemistry. Sixteen gains and thirty-two losses occurred in more than 30% and 60% of the tumors, respectively. High-level amplifications at 7q21.3-q22.1 and 19q13.2 and homozygous deletions at 1p33-p32.3, 1p22.1, 1q22, 3q27.2, 6p22.3, 6p21.31, 12q13.2, 17p13.2, 17q21.31 and 22q13.1 were identified. Especially, amplification of AKT2 was detected in two carcinomas and homozygous deletion of CDKN2C in other two cases. In 15 independent validation samples, we found that AKT2 (19q13.2) and MCM7 (7q22.1) were amplified in 6 and 9 cases, and CAMTA2 (17p13.2) and PFN1 (17p13.2) were homozygously deleted in 3 and 1 cases. AKT2 and MCM7 were overexpressed, and CAMTA2 and PFN1 were underexpressed in pancreatic cancer tissues than in morphologically normal operative margin tissues. Both GISTIC and Genomic Workbench software identified 22q13.1 containing APOBEC3A and APOBEC3B as the only homozygous deletion region. And the expression levels of APOBEC3A and APOBEC3B were significantly lower in tumor tissues than in morphologically normal operative margin tissues. Further validation showed that overexpression of PSCA was significantly associated with lymph node metastasis, and overexpression of HMGA2 was significantly associated with invasive depth of pancreatic cancer. These recurrent genomic changes may be useful for revealing the mechanism of pancreatic carcinogenesis and providing candidate biomarkers.
Bibliography:Conceived and designed the experiments: MRW ZZS. Performed the experiments: JWL ZZS TYS. Analyzed the data: JWL ZZS TYS XC. Contributed reagents/materials/analysis tools: ZW SSS XX YC PZ CFW ZXZ. Wrote the paper: JWL ZZS.
Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0114616