한빛사논문
- 조회723
Wungki Park 1, Catherine A O'Connor 1, Chaitanya Bandlamudi 1, Daniella Forman 2, Joanne F Chou 3, Shigeaki Umeda 4, Marsha Reyngold 5, Anna M Varghese 1, Fergus Keane 1, Fiyinfolu Balogun 1, Kenneth H Yu 6, David P Kelsen 6, Christopher Crane 7, Marinela Capanu 1, Christine Iacobuzio-Donahue 4, Eileen M O'Reilly 1
1Memorial Sloan Kettering Cancer Center, New York, NY, United States.
2Memorial Sloan Kettering Cancer Center, Philadelphia, PA, United States.
3Memorial Sloan Kettering Cancer Center, NYC, United States.
4Memorial Sloan Kettering Cancer Center, New York City, NY, United States.
5Memorial Sloan Kettering Cancer Center, United States.
6Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United States.
7Memorial Sloan Kettering, New York, NY, new york, United States.
W. Park, C.A. O'Connor, and E.M. O'Reilly contributed equally to this article.
Corresponding Author: Eileen M. O'Reilly
Abstract
Purpose: Characterizing germline and somatic ATM variants (gATMm, sATMm), zygosity and their contribution to homologous recombination deficiency (HRD) is important for therapeutic strategy in pancreas ductal adenocarcinoma (PDAC).
Methods: Clinico-genomic data for patients with PDAC and other cancers with ATM variants was abstracted. Genomic instability scores (GIS) were derived from ATM-mutant cancers and overall survival (OS) was evaluated.
Results: Forty-six patients with PDAC and pathogenic ATM variants including 24 (52%) stage III/IV; gATMm (N=24) and sATMm (N=22). Twenty-seven (59%) had biallelic, 15 (33%) monoallelic, and 4 indeterminate (8%) variants. Median OS for advanced stage cohort at diagnosis (N=24) was 19.7 months (95% CI: 12.3-NR); 27.1 months (95% CI: 22.7-NR) for gATMm (n=11) and 12.3 months for sATMm (n=13) (95% CI: 11.9-NR)) for sATMm (p=0.025). GIS was computed for 33 patients with PDAC and compared to other ATM-mutant cancers enriched for HRD. The median was lower (median, 11; range, 2-29) relative to breast (18, 3-55) or ovarian (25, 3-56) ATM-mutant cancers (p<0.001 and p=0.003, respectively). Interestingly, biallelic pathogenic ATM variants were mutually exclusive with TP53. Other canonical driver gene (KRAS, CDKN2A, SMAD4) variants were less frequent in ATM-mutant PDAC.
Conclusion: ATM variants in PDAC represent a distinct biologic group and appear to have favorable OS. Nonetheless, pathogenic ATM variants do not confer an HRD signature in PDAC and ATM should be considered as a non-core HR gene in this disease.
논문정보
- Research article
- 2022년 09월 (BRIC 등록일 2022-10-19)
- 국외 연구진
- 생명과학 > 노화/암생물학
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