Balla Agnes, Khan Farrah, Hampel Kenneth J, Aisner Dara L, Sidiropoulos Nikoletta
Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, Vermont 05401, USA.
Department of Hematology and Oncology, University of Vermont Medical Center, Burlington, Vermont 05401, USA.
Cold Spring Harb Mol Case Stud. 2018 Apr 2;4(2). doi: 10.1101/mcs.a002394. Print 2018 Apr.
Anaplastic lymphoma kinase (ALK) gene rearrangements are present in ∼5% of non-small-cell lung cancers (NSCLCs). These rearrangements occur because of a chromosomal inversion within the short arm of Chromosome 2, which results in the formation of the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion oncogene. Whereas NSCLC transformation to SCLC is a rare phenomenon described in epidermal growth factor receptor (EGFR) mutant cancers primarily after treatment with targeted therapy, it is exceedingly rare in ALK-rearranged adenocarcinomas. It is currently unclear what the therapeutic significance of the rearrangement is in this transformed tumor as there is a paucity of medical literature describing follow-up care and outcomes of patients in this rare scenario. We describe a unique case in which a patient with ALK-rearranged adenocarcinoma underwent small-cell transformation at a metastatic site with retained ALK rearrangement and was provided clinical follow-up after treatment with second-generation tyrosine kinase inhibiter (TKI) therapy.
间变性淋巴瘤激酶(ALK)基因重排在约5%的非小细胞肺癌(NSCLC)中存在。这些重排是由于2号染色体短臂内的染色体倒位所致,这导致了棘皮动物微管相关蛋白样4(EML4)-ALK融合致癌基因的形成。虽然NSCLC向小细胞肺癌(SCLC)的转化是一种罕见现象,主要在表皮生长因子受体(EGFR)突变型癌症接受靶向治疗后出现,但在ALK重排的腺癌中极为罕见。目前尚不清楚这种重排在这种转化肿瘤中的治疗意义,因为缺乏医学文献描述这种罕见情况下患者的后续治疗及结果。我们描述了一个独特病例,一名ALK重排腺癌患者在转移部位发生小细胞转化且ALK重排保留,在接受第二代酪氨酸激酶抑制剂(TKI)治疗后进行了临床随访。