Tissue-specific signatures of activating @entity10160 and RAS mutations in XXXX of gynecologic origin.

@entity1 @entity5 @entity984 @entity13374 @entity3909 @entity876 @entity5274 @entity3546 @entity8497 @entity10160 @entity4357 @entity6962
OBJECTIVES: Gynecologic @entity6962 is an aggressive @entity5 that requires more effective treatment approaches. However, therapeutic implications regarding the specific gynecologic site of origin and the admixture of @entity3909 that define this @entity5 remain uncertain. Therefore, broad genotyping was performed to identify tissue-specific somatic mutational profiles that may help direct targeted therapies in this complex @entity5 . METHODS: Genotyping was conducted on primary gynecologic @entity6962 arising from various disease sites (uterus, @entity5274 ) and within isolated histological subcomponents. Nucleic acids extracted from diagnostic tissue were used in a genotyping platform that simultaneously queried >120 common mutations across 14 @entity5 genes. Mutational status was correlated with clinical variables using logistic regression and Kaplan-Meier survival estimates. RESULTS: @entity5 gene mutations were identified in 46% of the 52 @entity1 cohort and include @entity876 (23%), @entity10160 (19%), @entity984 (15%), @entity3546 (4%) and @entity8497 (2%). Mutation in a single gene was observed in 31% of @entity1 samples, while synchronous mutations involving 2 and 3 genes were noted in 13% and 2% of samples, respectively. Comparative evaluation of the @entity3909 within a @entity5 demonstrated a similar mutation signature. Mutations in @entity10160 , @entity984 and @entity8497 were exclusive to @entity5 of uterine origin and age-adjusted Cox proportional hazards modeling associated advanced age, stage and @entity876 mutations with decreased survival in the uterine subset. CONCLUSION: While @entity6962 across @entity13374 sites are histologically similar, therapeutically relevant mutations in the mitogen-activated protein kinase and @entity4357 3-kinase pathways predominated in @entity6962 arising in the uterus.
