Prevalence of KRAS amplification in patients with metastatic cancer: Real-world next-generation sequencing analysis.
Pathol Res Pract
; 261: 155473, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-39106591
ABSTRACT
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 (2.5â¯%) had KRAS amplification. The highest frequency of KRAS amplification was detected in 2â¯% (27/1350) of patients with colorectal cancer, followed by 3.48â¯% (32/920) of patients with gastric cancer and 3.88â¯% (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, 27.3â¯% (27/99) had a concomitant KRAS mutation. More than 50â¯% of patients had G12D or G12V mutations. In gastric cancer, patients with both KRAS amplification and mutation were extremely rare at 3.1â¯% (1/32); however, in colorectal cancer, more than half of the patients had KRAS amplification and mutation (51.9â¯%, 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 (2.5â¯%) had KRAS amplification, and next-generation sequencing analysis provided a deeper understanding of KRAS amplification.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Amplificação de Genes
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Proteínas Proto-Oncogênicas p21(ras)
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Sequenciamento de Nucleotídeos em Larga Escala
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Proto-Oncogene Mas
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Mutação
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article