Genomic analysis of patient-derived xenograft models reveals intratumor-heterogeneity in endometrial cancer and can predict tumor growth inhibition with talazoparib

Study ID Alternative Stable ID Type
EGAS00001004666 Other

Study Description

Background: Endometrial cancer (EC) is a major gynecological cancer with increasing incidence. It comprised of four molecular subtypes with differing etiology, prognoses, and response to chemotherapy. In the future, clinical trials testing new single agents or combination therapies will be targeted to the molecular subtype most likely to respond. Pre-clinical models that faithfully represent the molecular subtypes of EC are urgently needed, we sought to develop and characterize a panel of novel EC patient-derived xenograft (PDX) models. Methods: Here, we report whole exome or whole genome sequencing of 11 PDX models and the matched primary tumor. Analysis of multiple PDX lineages and passages was performed to study tumor heterogeneity across lineages and/or passages. Based on recent reports of frequent defects in the homologous recombination (HR) pathway in EC, we assessed mutational signatures and HR deficiency scores and correlated these with in vivo responses to the PARP inhibitor (PARPi) talazoparib in six PDXs representing the copy number high/p53-mutant and mismatch-repair ... (Show More)

Study Datasets 2 datasets.

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Dataset ID Description Technology Samples
Whole genome and Whole exome sequencing of patient-derived xenograft models of endometrial cancer
HiSeq X Ten,Illumina HiSeq 2500,Illumina HiSeq 4000 50
SNP Array Data for EGAS00001004666
Illumina Global Screening Array-24 V1 HTS GSA+Multi-Disease 100

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