In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e17516-e17516
Abstract:
e17516 Background: DDR gene alterations(GAs) are prevalent in cancer and play key roles in tumorigenesis, progression and therapeutic response. However, the molecular profile of DDR in genitourinary cancer is still lacking in Asian. In this study, we assessed DDR GAs for better understanding therapeutic implications. Methods: Patients(pts) diagnosed with genitourinary cancer were enrolled. Tumors and plasma samples were collected for next-generation sequencing with Acornmed panel(2.0 Mbp) containing 808 cancer-related genes, including 34 DDR genes(Jonathan, et al.). OncoKB and COSMIC were used to identify GAs status including deleterious, unknown significance, and wild type(wt). Results: A total of 140 pts were enrolled with 56 pts of prostate cancer(PC), 55 pts of renal cell cancer(RCC) and 29 pts of urothelial cancer(UC). Metastatic diseases were accounted for 33.5%. A total of 127 tumor tissues and 109 baseline plasma samples were collected, including 96 matched tissue/plasma samples. A total of 109 pts(77.9%) harbored at least one GA in DDR pathway. UC carried the most DDR GAs(93.1 %), followed by PC(75%) and RCC(72.7%). After stratifying GA status, the most commonly deleterious GAs were ATM(n = 5); FANCA(n = 4); ERCC2, BRCA1, ATR, CHEK2(n = 2 each); MSH6, ERCC4, BRCA2, PALB2(n = 1 each).Tumor mutation burden(TMB) was significantly different among pts with deleterious, unknown significance and wt in PC(Mean: 17.8 vs 9.065 vs 4.468; p = 0.0003). Notably, DDR GAs were more likely to present in pts with metastatic disease(80.95% vs 62.50%), deleterious DDR GAs as well(14.29% vs 8.33%). Conclusions: DDR pathways are frequently altered in genitourinary cancer, especially UC in China. DDR GAs were significantly associated with higher TMB in PC. A higher prevalence was identified in metastatic disease. Comprehensive genomic profiling of DDR GAs highlights the clinical and therapeutic implication. Further exploration of the deleterious nature and alterations of unknown significance are required. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.e17516
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
