Department of Clinical Molecular Biology, Medical University of Bialystok, Bialystok, Poland.
Adv Med Sci. 2013;58(1):83-9. doi: 10.2478/v10039-012-0080-0.
In a retrospective analysis of the prevalence of KRAS mutations in patients with advanced non-small cell lung cancer (NSCLC), we detected a unique and not earlier described case of a double combination of mutations at codons 12 and 13 of the KRAS gene in a patient with lung adenocarcinoma.
MATERIAL/METHODS: To determine the molecular characteristics of the infrequent mutation and the mutational status of the KRAS gene in metastatic brain tumors in the same patient, we performed morphological and molecular tests.
Molecular analysis of the nature of the double mutation showed that the unique combination of variants is a monoallelic mutation. This type of changes has not yet been registered in the Catalogue of Somatic Mutations in Cancer database. Molecular assessment of the KRAS mutation status in the brain metastatic site in the same patient, showed no mutations in codons 12 and 13. Moreover, we did not find mutation at exon 19 and 21 of EGFR gene, both in primary tumor as well as in secondary metastatic foci in the brain.
The presented case shows an example of KRAS gene molecular mosaicism and heterogeneity of lung adenocarcinoma primary and metastatic tumors. Molecular heterogeneity of lung adenocarcinoma tumors can significantly affect eligibility of patients for targeted therapies.
在对晚期非小细胞肺癌（NSCLC）患者 KRAS 突变流行率的回顾性分析中，我们在肺腺癌患者中检测到 KRAS 基因密码子 12 和 13 处突变的独特且之前未描述的双重组合的一个病例。
材料/方法：为了确定该罕见突变的分子特征以及同一患者脑转移瘤中 KRAS 基因的突变状态，我们进行了形态学和分子检测。
对双突变性质的分子分析表明，这种独特的变体组合是单等位基因突变。这种类型的变化尚未在癌症体细胞突变目录数据库中登记。对同一患者脑转移部位 KRAS 突变状态的分子评估显示，在 12 和 13 密码子中没有突变。此外，我们在原发肿瘤和脑内继发性转移灶中均未发现 EGFR 基因外显子 19 和 21 的突变。
所提出的病例表明了 KRAS 基因分子镶嵌性和肺腺癌原发和转移性肿瘤异质性的一个例子。肺腺癌肿瘤的分子异质性可能会显著影响患者接受靶向治疗的资格。
