Molecular characterization of KRAS G12C mutation in the tumors of digestive system

Abstract

Abstract: Objective: To identified the molecular characteristics of KRAS G12C mutation in the tumors of digestive system.
Methods: Data of 1 100 patients diagnosed as digestive malignant tumor in Cancer Hospital of Chinese Academy of Medical Sciences from 2017 to 2022 were collected. The microsatellite status, tumor mutation burden (TMB) and KRAS, NRAS, BRAF and PIK3CA mutations were detected by next-generation sequencing in 1 100 patients with tumors of digestive system, including colorectal adenocarcinoma, duodenal adenocarcinoma, cholangiocarcinoma, gastric adenocarcinoma, ileocecal adenocarcinoma and pancreatic ductal adenocarcinoma.
Results: Microsatellite instability-high (MSI-H) tumors were most common in duodenal adenocarcinoma (19%), followed by ileocecal adenocarcinoma (18%) and colorectal adenocarcinoma (10.2%). However, no MSI-H tumors were detected in the 100 cases of pancreatic ductal adenocarcinoma. TMB values also varied among different tumors of digestive system. High-TMB (≥10 mut/Mb) tumors were most common in ileocecal adenocarcinoma (24%), followed by duodenal adenocarcinoma (22%) and gastric adenocarcinoma (18.9%). KRAS mutations were detected in 452 of 1 100 (41.09%) cases, among which the most common tumor was pancreatic ductal adenocarcinoma (85.0%), followed by duodenal adenocarcinoma (56%) and ileocecal adenocarcinoma (53%). However, KRAS mutations were identified in 7.3% of gastric adenocarcinoma. KRAS G12C mutation was detected in 2.82% of all the 1 100 tumors, and only 6.9% (31/452) of all digestive tumors with KRAS mutations among which the most common tumor was ileocecal adenocarcinoma (2/9), followed by duodenal adenocarcinoma (13%) and colorectal adenocarcinoma (8.8%). However, no significant differences in gender, age, MSI and TMB status were observed between patients with KRAS G12C mutation and other KRAS mutation subtypes.
Conclusions: Although nearly half of patients with digestive malignancies carry KRAS mutations, but only 6.9% of KRAS-mutant cases harbored KRAS G12C mutation subtype. KRAS G12C mutation was most common in ileocecal cancer, duodenal cancer and colorectal cancer. And no obvious difference in clinical and molecular pathological features compared with other types of KRAS mutations

Key words: Tumors of digestive system, Next-generation sequencing, KRAS G12C mutation

Zhao Tingqi, Dong Lin, Ying Jianming, Li Weihua. Molecular characterization of KRAS G12C mutation in the tumors of digestive system[J]. Electronic Journal of Liver Tumor, 2024, 11(1): 4-8.

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