Multiomic Analysis of Lung Tumors Defines Pathways Activated in Neuroendocrine Transformation.

ABSTRACT: Lineage plasticity is implicated in treatment resistance in multiple cancers. In lung adenocarcinomas (LUAD) amenable to targeted therapy, transformation to small cell lung cancer (SCLC) is a recognized resistance mechanism. Defining molecular mechanisms of neuroendocrine (NE) transformation in lung cancer has been limited by a paucity of pre/posttransformation clinical samples. Detailed genomic, epigenomic, transcriptomic, and protein characterization of combined LUAD/SCLC tumors, as well as pre/posttransformation samples, supports that NE transformation is primarily driven by transcriptional reprogramming rather than mutational events. We identify genomic contexts in which NE transformation is favored, including frequent loss of the 3p chromosome arm. We observed enhanced expression of g

SUBMITTER: Quintanal-Villalonga A 

PROVIDER: S-EPMC9437746 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature