Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival.

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Tác giả: Fiyinfolu Balogun, Chaitanya Bandlamudi, Olca Basturk, Michael F Berger, A Rose Brannon, Marinela Capanu, Debyani Chakravarty, Joanne F Chou, Amanda Erakky, Christopher Fong, Christine A Iacobuzio-Donahue, William R Jarnagin, David P Kelsen, Diana Mandelker, Miika Mehine, Daniel Muldoon, Subhiksha Nandakumar, Bastien Nguyen, Eileen M O'Reilly, Wungki Park, Maria A Perry, Mark A Schattner, Nikolaus Schultz, Zsofia K Stadler, Efsevia Vakiani, Anna M Varghese, Alice C Wei, Kenneth H Yu, Amanda Zucker

Ngôn ngữ: eng

Ký hiệu phân loại: 636.0885 Animal husbandry

Thông tin xuất bản: United States : Nature medicine , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 189679

Nearly all pancreatic adenocarcinomas (PDAC) are genomically characterized by KRAS exon 2 mutations. Most patients with PDAC present with advanced disease and are treated with cytotoxic therapy. Genomic biomarkers prognostic of disease outcomes have been challenging to identify. Herein leveraging a cohort of 2,336 patients spanning all disease stages, we characterize the genomic and clinical correlates of outcomes in PDAC. We show that a genomic subtype of KRAS wild-type tumors is associated with early disease onset, distinct somatic and germline features, and significantly better overall survival. Allelic imbalances at the KRAS locus are widespread. KRAS mutant allele dosage gains, observed in one in five (20%) KRAS-mutated diploid tumors, are correlated with advanced disease and demonstrate prognostic potential across disease stages. With the rapidly expanding landscape of KRAS targeting, our findings have potential implications for clinical practice and for understanding de novo and acquired resistance to RAS therapeutics.
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