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The clinicopathological characteristics of co-mutations in exon 2 and 3 of the KRAS gene in patients with colorectal cancer

克拉斯 外显子 结直肠癌 基因 癌症研究 医学 突变 癌症 肿瘤科 遗传学 内科学 生物
作者
Huizhen Peng,Hong‐Tian Yao,Xiaojun Jiang,Huijuan Zhu,Jun Li,Hui Tang
出处
期刊:Pathology Research and Practice [Elsevier BV]
卷期号:270: 155990-155990
标识
DOI:10.1016/j.prp.2025.155990
摘要

KRAS, one of the most frequently mutated oncogenes in colorectal cancer (CRC), with mutations in approximately 40 % of all CRC cases. KRAS mutations exhibit considerable diversity. Studies have shown that patients with mutations at codon 13 (G13) of the KRAS gene have a higher risk of mortality, while mutations at codon 12 (G12) of the KRAS gene are also associated with prognosis, though their impact on mortality risk is lower than that of codon 13 mutations. Therefore, identifying the specific KRAS mutation type is crucial for assessing patient prognosis and developing personalized treatment plans. KRAS mutations typically occur in a single exon, whereas co-mutations in exon 2 (G12/G13) and exon 3 (Q61) in a single tissue haven't been reported yet. In this study, we reported a co-mutation in two exons (exon 2 and exon 3) of the KRAS gene in a 72-year-old male with CRC, adenocarcinoma located at 8 cm from the anus. NGS and ARMS-PCR revealed that two exons of KRAS were co-mutated in this patient-- Q61H in exon 3, with a mutation frequency of 21.09 % and G13D in exon 2, with a variance frequency of 6.06 %. A copy number increase (copy number: 5.65) in MET gene was also found in this patient simultaneously. The clinicopathological characteristics were analyzed, and the possible mechanisms were further discussed. However, due to the CRC patients with co-mutations in two exons of the KRAS are exceedingly rare, a cohort study with more patients' clinical data is urged.
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