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Oncogenic mutations in cervical cancer
Author(s) -
Wright Alexi A.,
Howitt Brooke E.,
Myers Andrea P.,
Dahlberg Suzanne E.,
Palescandolo Emanuele,
Hummelen Paul,
MacConaill Laura E.,
Shoni Melina,
Wagle Nikhil,
Jones Robert T.,
Quick Charles M.,
Laury Anna,
Katz Ingrid T.,
Hahn William C.,
Matulonis Ursula A.,
Hirsch Michelle S.
Publication year - 2013
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.28288
Subject(s) - kras , neuroblastoma ras viral oncogene homolog , cervical cancer , medicine , genotyping , cancer research , cancer , adenocarcinoma , hras , mutation , hazard ratio , oncology , epidermal growth factor receptor , genotype , gene , biology , confidence interval , genetics , colorectal cancer
BACKGROUND Cervical cancer is the second leading cause of cancer deaths among women worldwide. The objective of this study was to describe the most common oncogenic mutations in cervical cancers and to explore genomic differences between the 2 most common histologic subtypes: adenocarcinoma and squamous cell carcinoma. METHODS A high‐throughput genotyping platform, termed Oncomap, was used to interrogate 80 cervical tumors for 1250 known mutations in 139 cancer genes. Samples were analyzed using a mass spectrometry‐based genotyping platform and were validated using orthogonal chemistry. Epidermal growth factor receptor ( EGFR ) mutations were further validated by massive parallel sequencing. Human papilloma virus (HPV) genotyping also was performed. RESULTS Validated mutations were detected in 48 of 80 tumors (60%) examined. The highest mutation rates were in the genes phosphatidylinositol 3‐kinase, catalytic subunit α ( PIK3CA ) (31.3%); Kirsten rat sarcoma viral oncogene homolog ( KRAS ) (8.8%); and EGFR (3.8%). PIK3CA mutation rates did not differ significantly between adenocarcinomas and squamous cell carcinomas (25% vs 37.5%, respectively; P = .33). In contrast, KRAS mutations were identified only in adenocarcinomas (17.5% vs 0%; P = .01), and a novel EGFR mutation was detected only in squamous cell carcinomas (0% vs 7.5%; P = .24). There were no associations between HPV‐16 or HPV‐18 and somatic mutations or overall survival. In adjusted analyses, PIK3CA mutations were associated with shorter survival (67.1 months vs 90.3 months; hazard ratio, 9.1; 95% confidence interval, 2.8‐29.5 months; P < .001). CONCLUSIONS Cervical cancers harbor high rates of potentially targetable oncogenic mutations. In addition, cervical squamous cell carcinoma and adenocarcinoma have distinct molecular profiles, suggesting that clinical outcomes may be improved with the use of more tailored treatment strategies, including PI3K and MEK inhibitors. Cancer 2013;119:3776–3783. © 2013 American Cancer Society.