Real-World comprehensive genomic profiling data for diagnostic clarity in pulmonary Large-Cell neuroendocrine carcinoma

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2024-02, Vol.188, p.107454-107454, Article 107454
• Main Authors: Burns, Laura, Tukachinsky, Hanna, Raskina, Kira, Huang, Richard S P, Schrock, Alexa B, Sands, Jacob, Kulke, Matthew H, Oxnard, Geoffrey R, Tapan, Umit
• Format: Article
• Language: English
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2023.107454

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is an uncommon subtype of lung cancer believed to represent a spectrum of tumors sharing characteristics of both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Other groups have proposed genomic LCNEC subtypes, including small cell-like, non-small cell-like, and carcinoid-like subtypes. The primary goal of this study was to better define the NSCLC-like subtype with comprehensive genomic profiling (CGP). An institutional database was queried to identify tissue specimens (TBx, N = 1,426) and liquid biopsies (LBx, N = 39) submitted for CGP during routine clinical care (8/2014 - 7/2023) with a disease ontology of LCNEC. TBx were profiled with FoundationOne® (F1) or F1CDx, using hybrid-capture technology to detect genomic alterations (GAs). 1,426 LCNEC samples were genomically profiled. The presence of RB1 and TP53 genomic alterations (GAs) were used to define a SCLC-like subtype (n = 557). A carcinoid-like group was defined by the presence of MEN1 mutation in the absence of TP53 GAs (n = 25). The remaining 844 samples were compared to the SCLC-like group and GAs enriched relative to the SCLC-like samples with a false discovery rate (FDR)