Introduction
Neuroendocrine transformation has been reported in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) patients after ALK inhibition, but unlike epidermal growth factor receptor (EGFR)-mutant NSCLC, the exact mechanism of neuroendocrine (NE) transformation in ALK-rearranged NSCLC is poorly studied.
Methods
We collected the matched pre- and post-transformation samples from a patient with ALK-rearranged lung adenocarcinoma (LUAD) and performed targeted panel sequencing, whole-exome sequencing (WES) and bulk RNA sequencing.
Results
Multiple mutations were shared between the pre- and post-transformation samples. Neither RB1 nor TP53 mutation was detected, but CDKN2A deletion and CDK4 amplification were found instead. Mismatch repair (MMR)-associated mutational signature was significantly enriched after transformation. Genes associated with Notch signaling and PI3K/AKT pathway were significantly upregulated, whereas genes related to lymphocyte activation and NF-kappa B signaling were downregulated. Signatures relating to homologous recombination (HR), MMR and Notch signaling pathway were enriched, which were further validated in TCGA cohorts. Macrophages M2 showed prominently higher abundance in the tumor immune microenvironment after NE transformation.
Conclusions
The mechanism of NE transformation in ALK-rearranged LUAD may be different from that in EGFR-mutant LUAD. READ ARTICLE
JTO Clinical and Research Reports DOI:10.1016/j.jtocrr.2022.100338
Authors: Jie Huang, Shi-Ling Zhang, Chaozheng Zhou, Weiye Huang, Peng Luo, Hua-Jun Chen, Jin-Ji Yang,