Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Rio de Janeiro 20231-092, Brazil.
Oncoclínicas, São Paulo 22251-060, Brazil.
Medicina (Kaunas). 2021 Sep 29;57(10):1039. doi: 10.3390/medicina57101039.
: One of the most frequently mutated oncogenes in cancer belongs to the Ras family of proto-oncogenes, which encode distinct key signaling events. RAS gain-of-function mutations are present in ~30% of all human cancers, with KRAS being the most frequently mutated isoform showing alterations in different cancer types including lung cancer. This study aimed to investigate the incidence of KRAS mutations, and concomitant mutations, in advanced non-small cell lung adenocarcinoma patients. : This was a retrospective study, where genomic DNA extracted from paraffin-embedded tumor tissues from 121 Brazilian advanced non-small cell lung adenocarcinoma patients were analyzed to evaluate via Next Generation Sequencing (NGS) the incidence of KRAS mutations and co-occurring mutations and correlate, when possible, to clinicopathological characteristics. Statistical analyses were performed to calculate the prevalence of mutations and to investigate the association between mutational status, mutation type, and sex. : The results showed a prevalence of male (N = 63; 54.8%) compared to female patients (N = 52, 45.2%), and mutant KRAS was present in 20.86% (24/115) of all samples. Interestingly, 33.3% of the mutant KRAS samples showed other mutations simultaneously. : This study revealed the presence of rare KRAS concomitant mutations in advanced lung adenocarcinoma patients. Further investigation on the importance of these genomic alterations in patient prognosis and treatment response is warranted.
在癌症中,最常发生突变的癌基因之一属于原癌基因 Ras 家族,该家族编码独特的关键信号事件。RAS 功能获得性突变存在于约 30%的所有人类癌症中,其中 KRAS 是最常发生突变的同工型,在包括肺癌在内的不同癌症类型中发生改变。本研究旨在调查晚期非小细胞肺腺癌患者中 KRAS 突变及其伴随突变的发生率。
这是一项回顾性研究,对 121 名巴西晚期非小细胞肺腺癌患者的石蜡包埋肿瘤组织中的基因组 DNA 进行了分析,通过下一代测序 (NGS) 评估 KRAS 突变和伴随突变的发生率,并尽可能与临床病理特征相关联。进行了统计分析以计算突变的流行率,并研究突变状态、突变类型和性别之间的关联。
结果显示,男性患者(N = 63;54.8%)多于女性患者(N = 52,45.2%),所有样本中突变型 KRAS 的患病率为 20.86%(24/115)。有趣的是,33.3%的突变型 KRAS 样本同时存在其他突变。
本研究揭示了晚期肺腺癌患者中罕见的 KRAS 伴随突变的存在。需要进一步研究这些基因组改变对患者预后和治疗反应的重要性。