Kojitani Yoshiki, Sakai Daisuke, Ogata Takatsugu, Amano Yumi, Mori Ryota, Kitakaze Masatoshi, Sueda Toshinori, Otsuka Tomoyuki, Nishio Minako, Ishihara Mikiya, Kagawa Yoshinori, Nishimura Junichi, Sugimoto Naotoshi, Yagi Toshinari, Takeda Masayuki, Yasui Masayoshi, Kudo Toshihiro
Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Osaka 541-8567, Japan.
Department of Cancer Genomics and Medical Oncology, Nara Medical University, Kashihara, Nara 634-8521, Japan.
Oncol Lett. 2025 Jun 2;30(2):377. doi: 10.3892/ol.2025.15123. eCollection 2025 Aug.
Metastatic colorectal cancer (mCRC) presents notable therapeutic challenges. Rat sarcoma virus () mutations, including those in exon 2, are critical for treatment decisions; however, the role of minor mutations ( exons 3 and 4, and ) remains underexplored. Because these mutations are increasingly identified in routine practice due to advances in mutation testing that now routinely includes exons 3 and 4, and , clarifying their clinical relevance has become important for ensuring appropriate treatment selection. The present study aimed to compare the clinical and prognostic characteristics of patients with mCRC with minor mutations to those with exon 2 mutations. To this end, data were retrospectively collected from patients with mCRC and mutations between August 2018 and December 2023. Patients were grouped based on mutation subtype: exon 2 or minor mutations. mutation testing was performed using the MEBGEN RASKET™-B kit. Clinical characteristics, tumor location, metastatic patterns and survival outcomes were analyzed. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazards regression models. Of 202 patients with mutations, 170 had exon 2 mutations, whereas 32 exhibited minor mutations (20 with non-exon 2 mutations and 12 with mutations). Minor mutations were more common in left-sided CRC. No significant differences in background were observed between the two groups. Log-rank OS was comparable for patients with exon 2 and minor mutations. OS and PFS with first-line bevacizumab-containing therapy were also similar between the two groups. In conclusion, the prognostic impact of minor mutations appears to be comparable to that of exon 2 mutations, suggesting that the current treatment strategies for -mutant CRC may not require modification based on these findings.
转移性结直肠癌(mCRC)面临着显著的治疗挑战。鼠肉瘤病毒()突变,包括第2外显子中的突变,对治疗决策至关重要;然而,次要的突变(第3和4外显子以及中的突变)的作用仍未得到充分探索。由于现在常规检测包括第3和4外显子以及中的突变,使得这些突变在常规实践中越来越多地被识别出来,因此明确它们的临床相关性对于确保合适的治疗选择变得很重要。本研究旨在比较具有次要突变的mCRC患者与具有第2外显子突变的患者的临床和预后特征。为此,回顾性收集了2018年8月至2023年12月期间患有mCRC和突变的患者的数据。根据突变亚型对患者进行分组:第2外显子突变或次要突变。使用MEBGEN RASKET™-B试剂盒进行突变检测。分析临床特征、肿瘤位置、转移模式和生存结果。使用Kaplan-Meier生存分析、对数秩检验和Cox比例风险回归模型评估总生存期(OS)和无进展生存期(PFS)。在202例有突变的患者中,170例有第2外显子突变,而32例表现出次要突变(20例为非第2外显子突变,12例为突变)。次要突变在左侧结直肠癌中更常见。两组之间在背景方面未观察到显著差异。第2外显子突变和次要突变患者的对数秩OS相当。两组之间一线含贝伐单抗治疗的OS和PFS也相似。总之,次要突变的预后影响似乎与第2外显子突变相当,这表明目前针对突变型结直肠癌的治疗策略可能无需基于这些发现进行修改。