Mengoli Maria Cecilia, Barbieri Fausto, Bertolini Federica, Tiseo Marcello, Rossi Giulio
Unit of Pathology, University Hospital Policlinico, Modena, Italy.
Operative Unit of Oncology, University Hospital Policlinico, Modena, Italy.
Lung Cancer. 2016 Mar;93:55-8. doi: 10.1016/j.lungcan.2016.01.002. Epub 2016 Jan 11.
The paradigm of mutually exclusive alterations among oncogenic drivers in non-small-cell lung cancer (NSCLC) is challenged by the increasing evidence of detection of two or more driver alterations in the same tumor using highly-sensitive molecular assays. We report here two cases of ALK-rearranged adenocarcinomas harboring concomitant exon 2 K-RAS mutations (G13D and Q61H). The patients, a 49-year-old smoker man and a 59-year-old non-smoking woman, experienced a rapid disease progression and primary resistance to crizotinib. Search for similar cases in the literature reveals that concomitant K-RAS mutations and ALK rearrangement occur in a subset of NSCLC and seems to lead to resistance to crizotinib. Among 8 similar cases receiving crizotinib previously reported (4 in first line and 4 in second line), 1 had a partial response, 1 stable disease and 6 disease progression. One patient still had progression disease when switching to ceritinib. At the end, K-RAS mutations seem to represent a negative predictive marker in ALK-rearranged adenocarcinomas treated with ALK inhibitor.
非小细胞肺癌（NSCLC）致癌驱动因素之间相互排斥性改变的模式受到了挑战，越来越多的证据表明，使用高灵敏度分子检测方法可在同一肿瘤中检测到两种或更多种驱动因素改变。我们在此报告两例ALK重排腺癌病例，同时伴有第2外显子K-RAS突变（G13D和Q61H）。这两名患者，一名49岁的吸烟男性和一名59岁的非吸烟女性，均经历了疾病的快速进展以及对克唑替尼的原发性耐药。在文献中搜索类似病例发现，K-RAS突变与ALK重排在一部分NSCLC中同时出现，似乎会导致对克唑替尼耐药。在先前报道的8例接受克唑替尼治疗的类似病例中（4例一线治疗，4例二线治疗），1例部分缓解，1例病情稳定，6例病情进展。1例患者在换用色瑞替尼时仍有疾病进展。最后，K-RAS突变似乎是接受ALK抑制剂治疗的ALK重排腺癌中的一个阴性预测标志物。
