Laboratory of Molecular and Cellular Haematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Mol Biol Rep. 2013 Jun;40(6):4109-14. doi: 10.1007/s11033-013-2512-8. Epub 2013 May 3.
Mutations in the KRAS gene have been shown to play a key role in the pathogenesis of a variety of human tumours. However the mutational spectrum of KRAS gene differs by organ site. In this study, we have analysed the mutational spectrum of KRAS exon 1 in bladder tumours, colorectal cancer (CRC) and chronic myeloid leukemia (CML). A total of 366 patients were included in the present study (234 bladder tumours, 48 CRC and 84 CML). The KRAS mutations are absent in BCR/ABL1 positive CML. This result suggests that BCR/ABL1 fusion gene and KRAS mutations were mutually exclusive. The frequency of KRAS mutations in bladder cancer was estimated at 4.27 %. All of mutations were found in codon 12 and 90 % of them were detected in advanced bladder tumours. However the correlation between KRAS mutations and tumour stage and grade does not report a statistical significant association. The KRAS mutations occur in 35.41 % of patients with CRC. The most frequent mutations were G12C, G12D and G13D. These mutations were significantly correlated with histological differentiation of CRC (p = 0.024). Although the high frequency of KRAS in CRC in comparison to bladder cancer, these two cancers appear to have the same mutational spectrum (p > 0.05).
KRAS 基因突变已被证明在多种人类肿瘤的发病机制中发挥关键作用。然而，KRAS 基因突变谱因器官部位而异。在这项研究中，我们分析了膀胱癌、结直肠癌（CRC）和慢性髓性白血病（CML）中 KRAS 外显子 1 的突变谱。本研究共纳入 366 例患者（234 例膀胱癌、48 例 CRC 和 84 例 CML）。BCR/ABL1 阳性的 CML 中不存在 KRAS 突变。这一结果表明 BCR/ABL1 融合基因和 KRAS 突变是相互排斥的。膀胱癌中 KRAS 突变的频率估计为 4.27%。所有突变均发生在密码子 12 位，其中 90%发生在晚期膀胱癌中。然而，KRAS 突变与肿瘤分期和分级之间的相关性没有统计学意义。CRC 患者中 KRAS 突变的发生率为 35.41%。最常见的突变为 G12C、G12D 和 G13D。这些突变与 CRC 的组织学分化显著相关（p=0.024）。尽管 CRC 中 KRAS 的频率高于膀胱癌，但这两种癌症似乎具有相同的突变谱（p>0.05）。
