Abstract B036: Allele Specific Characteristics of KRAS Q61 Mutated Gastrointestinal Malignancies and Clinical Outcomes and Transcriptomic Features

作者：Salem Khoury, Mahmoud Yousef, Abdelrahman Yousef, Saikat Chowdhury, Ryan Lewis, Paul Roy, Jarret Feldman, Brandon G. Smaglo, Robert A. Wolff, Shubham Pant, Jason Willis, Maria Pia Morelli, Ryan Huey, Michael J. Overman, Huili Zhu, S Daniel Haldar, Camila Bragança Xavier, Nicole Balmaceda, Camila Lopez, Anthony Chen, Ethan B. Ludmir, Eugene J. Koay, Rebecca Snyder, Matthew H. G. Katz, Sophia Ren, Huamin Wang, John Paul Shen, Dan Zhao · 发表于：Clinical Cancer Research · 年份：2026 · DOI：10.1158/1557-3265.d32026-b036 · 研究领域：Medicine、Cancer research、Internal medicine、Oncology

Abstract Background: Pan-RAS inhibition is actively entering clinical practice with pan-KRAS and allele specific inhibitors in clinical development. Understanding allele specific features of KRAS mutations is critical for KRAS targeted therapy. KRAS Q61 is rare and less studied. Here we investigate the clinical and molecular features of KRAS Q61 mutated gastrointestinal (GI) malignancies with a focus on pancreatic cancer. Methods: We used the Palantir Foundry system to query clinical and molecular information with overall survival (OS) data of patients diagnosed with colorectal (CRC), pancreatic adenocarcinoma (PDAC), appendiceal (AA), cholangiocarcinoma (CC), hepatocellular carcinoma (HCC) and gastroesophageal cancer whose tumors were tested for KRAS mutations at our institution between 2002-2025. A subset of PDAC (N=145) who had bulk RNA sequencing were analyzed and an external cohort of 578 PDAC patients were used for validation. Results: KRAS mutation was tested in 13,535 patient tumors at MDA. KRAS was mutated in 46.4% (n= 4,516) of CRC, 87.1% of PDAC (n=1,357), 18.4% of CC (n=100), 50.3% of AA (n=393), 7.3% of gastroesophageal carcinoma (n=51) and 7.4% of HCC (n=16). KRAS Q61 consisted of 5.3% (n=340) of KRAS mutation (n= 6,433). KRAS Q61H was the most common KRAS Q61 allele. The top co-mutated genes with KRAS were TP53 (71%) and APC (63%) for CRC, TP53 (76%) and CDKN2A (28%) for PDAC, GNAS (34%) and TP53 (34%) for AA and TP53 (30%) and ARID1A (19%) for CC. Patients wit...