Prevalence of KRAS amplification in patients with metastatic cancer: Real-world next-generation sequencing analysis.

Autor: Choi DH; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Jang HL; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea., Lim SH; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Kim ST; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Hong JY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Park SH; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Park JO; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Kim DG; Department of Clinical Genomic Center, Samsung Medical Center, Seoul 06351, South Korea; Department of Digital Health, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul 06351, South Korea., Kim KM; Department of Pathology and Translational Genomics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea., Lee J; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: jyunlee@skku.edu.
Jazyk: angličtina
Zdroj: Pathology, research and practice [Pathol Res Pract] 2024 Sep; Vol. 261, pp. 155473. Date of Electronic Publication: 2024 Jul 24.
DOI: 10.1016/j.prp.2024.155473
Abstrakt: Background: The Kirsten rat sarcoma virus (KRAS) is a prominent proto-oncogene. Several treatments for KRAS mutations have been developed. However, KRAS amplification, a KRAS alteration, is poorly understood, and there is currently no appropriate treatment other than conventional chemotherapy. This study aimed to elucidate the role of KRAS amplification in different types of cancers.
Methods: From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3895 patients with 37 different cancer types at the Samsung Medical Center. We analyzed the distribution of KRAS amplification according to cancer type and its correlation with tumor mutation burden (TMB). Concomitant KRAS mutations were also identified.
Results: Of the total 3895 patients, 99 (2.5 %) had KRAS amplification. The highest frequency of KRAS amplification was detected in 2 % (27/1350) of patients with colorectal cancer, followed by 3.48 % (32/920) of patients with gastric cancer and 3.88 % (9/232) patients with of pancreatic cancer. MSI-High was not detected in patients with KRAS amplification. There was no correlation between KRAS copy number variation and TMB status. Among patients with KRAS amplification, 27.3 % (27/99) had a concomitant KRAS mutation. More than 50 % of patients had G12D or G12V mutations. In gastric cancer, patients with both KRAS amplification and mutation were extremely rare at 3.1 % (1/32); however, in colorectal cancer, more than half of the patients had KRAS amplification and mutation (51.9 %, 14/27). KRAS amplification and mutations are associated with mutations in tumor suppressor genes TP53, BRCA2, ARID1B, and PTCH1.
Conclusions: Of the 3895 patients with metastatic solid tumors, 99 (2.5 %) had KRAS amplification, and next-generation sequencing analysis provided a deeper understanding of KRAS amplification.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier GmbH.)
Databáze: MEDLINE
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