Abudabous Asma, Drah Mustafa, Aldehmani Mamdouh, Parker Iqbal, Alqawi Omar
Department of Life Sciences, The Libyan Academy, Misurata 218-51, Libya.
Department of Zoology, Faculty of Science, Misurata University, Misurata 218-51, Libya.
Mol Clin Oncol. 2021 Oct;15(4):197. doi: 10.3892/mco.2021.2359. Epub 2021 Jul 30.
Large prospective clinical trials have demonstrated that colorectal cancers (CRCs) with wild-type KRAS respond favorably to anti-epidermal growth factor receptor treatment, thus making mutational analysis obligatory prior to treatment. In our study, frozen CRC tissues from Libyan patients were analyzed for KRAS and HRAS mutations in codons 12/13 by direct sequencing and the correlations with clinical and pathological parameters were investigated. A total of 34 CRC cases, comprising 19 men and 15 women (age range, 24-87 years), were subjected to systematic analysis for RAS mutations. Although HRAS mutations were not detected in any of the patients in the study group, KRAS codon 12/13 mutations were present in 38.2% (13/34) of the patients. The frequent types of codon 12 mutations were glycine to aspartate (G12D, 46.1%); glycine to valine (G12V, 30.8%) and glycine to cysteine (G12C, 15.4%), while the codon 13 mutations were glycine to aspartate (G13D, 7.7%). G→A mutations occurred in 53.8% (7/13) of the patients, while G→T mutations occurred in 46.2% (6/13) of the patients. Mutations occurred at the first base of codon 12 or 13 in 2/13 (15.4%) and at the second base in 11/13 (84.6%) patients. There was no significant association between clinicopathological characteristics and KRAS mutation status, except the site of the tumors harboring KRAS mutations, which was as follows: The frequency was higher among tumors located in the left colon (8/13, 61.5%) compared to other sites (P=0.027). KRAS mutations were correlated with advanced age, with 10/13 being aged >50 years and affected 8/15 female patients (53%) compared with 5/19 male patients (26%). The highest frequency of KRAS mutations was observed in highly differentiated CRCs (8/13).
大型前瞻性临床试验表明，具有野生型KRAS的结直肠癌（CRC）对抗表皮生长因子受体治疗反应良好，因此在治疗前进行突变分析是必不可少的。在我们的研究中，通过直接测序分析了来自利比亚患者的冷冻CRC组织中密码子12/13的KRAS和HRAS突变，并研究了其与临床和病理参数的相关性。共有34例CRC病例，包括19名男性和15名女性（年龄范围为24 - 87岁），接受了RAS突变的系统分析。虽然在研究组的任何患者中均未检测到HRAS突变，但38.2%（13/34）的患者存在KRAS密码子12/13突变。密码子12突变的常见类型为甘氨酸突变为天冬氨酸（G12D，46.1%）；甘氨酸突变为缬氨酸（G12V，30.8%）和甘氨酸突变为半胱氨酸（G12C，15.4%），而密码子13突变为甘氨酸突变为天冬氨酸（G13D，7.7%）。53.8%（7/13）的患者发生G→A突变，46.2%（6/13）的患者发生G→T突变。12/13（15.4%）的患者在密码子12或13的第一个碱基发生突变，11/13（84.6%）的患者在第二个碱基发生突变。除了携带KRAS突变的肿瘤部位外，临床病理特征与KRAS突变状态之间没有显著关联，具体情况如下：位于左结肠的肿瘤中突变频率较高（8/13，61.5%），与其他部位相比（P = 0.027）。KRAS突变与高龄相关，13例中有10例年龄>50岁，15例女性患者中有8例（53%）受影响，而19例男性患者中有5例（26%）。在高分化CRC中观察到KRAS突变频率最高（8/13）。
