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Cancer DOI:10.1002/cncr.28288

Oncogenic mutations in cervical cancer: genomic differences between adenocarcinomas and squamous cell carcinomas of the cervix.

Publication TypeJournal Article
Year of Publication2013
AuthorsWright, AA, Howitt, BE, Myers, AP, Dahlberg, SE, Palescandolo, E, Van Hummelen, P, MacConaill, LE, Shoni, M, Wagle, N, Jones, RT, Quick, CM, Laury, A, Katz, IT, Hahn, WC, Matulonis, UA, Hirsch, MS
JournalCancer
Volume119
Issue21
Pages3776-83
Date Published2013 Nov 01
ISSN1097-0142
KeywordsAdenocarcinoma, Adult, Carcinoma, Squamous Cell, Cohort Studies, DNA Mutational Analysis, Female, Gene Frequency, Genes, erbB-1, Genotype, Humans, Middle Aged, Mutation, Oncogenes, Phosphatidylinositol 3-Kinases, SEER Program, Uterine Cervical Neoplasms
Abstract

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

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.

URLhttp://dx.doi.org/10.1002/cncr.28288
DOI10.1002/cncr.28288
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24037752?dopt=Abstract

Alternate JournalCancer
PubMed ID24037752
PubMed Central IDPMC3972000
Grant ListK07 CA166210 / CA / NCI NIH HHS / United States
K23 MH097667 / MH / NIMH NIH HHS / United States
T32 CA009172 / CA / NCI NIH HHS / United States