Cancers, Vol. 13, Pages 4572: Genomic Determinants of Homologous Recombination Deficiency across Human Cancers
Cancers, Vol. 13, Pages 4572: Genomic Determinants of Homologous Recombination Deficiency across Human Cancers
Cancers doi: 10.3390/cancers13184572
Authors:
Tao Qing
Xinfeng Wang
Tomi Jun
Li Ding
Lajos Pusztai
Kuanlin Huang
Germline BRCA1/2 mutations associated with HRD are clinical biomarkers for sensitivity to poly-ADP ribose polymerase inhibitors (PARPi) treatment in breast, ovarian, pancreatic, and prostate cancers. However, it remains unclear whether other mutations may also lead to HRD and PARPi sensitivity across a broader range of cancer types. Our goal was to determine the germline or somatic alterations associated with the HRD phenotype that might therefore confer PARPi sensitivity. Using germline and somatic genomic data from over 9000 tumors representing 32 cancer types, we examined associations between HRD scores and pathogenic germline variants, somatic driver mutations, and copy number deletions in 30 candidate genes involved in homologous recombination. We identified several germline and somatic mutations (e.g., BRCA1/2, PALB2, ATM, and ATR mutations) associated with HRD phenotype in ovarian, breast, pancreatic, stomach, bladder, and lung cancer. The co-occurrence of germline BRCA1 variants and somatic TP53 mutations was significantly associated with increasing HRD in breast cancer. Notably, we also identified multiple somatic copy number deletions associated with HRD. Our study suggests that multiple cancer types include tumor subsets that s...
Source: Cancers - Category: Cancer & Oncology Authors: Tao Qing Xinfeng Wang Tomi Jun Li Ding Lajos Pusztai Kuanlin Huang Tags: Article Source Type: research
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