Journal of Carcinogenesis & Mutagenesis

Abstract

Genetic Alterations and Tumor Mutation Burden of Poorly Differentiated Small Cell Euro-endocrine Carcinomas are Similar in Lung Lesions and Distant Metastatic Foci

Omid S Tehrani, Philip J Stephens, Garrett M Frampton, Caitlin F Connelly, Ethan S Sokol, Jeffrey S Ross, Vincent A Miller and Jackie Moriarty

Objective: Studying the genetic alterations of poorly differentiated small cell neuroendocrine carcinomas to improve the understanding of the biology of these aggressive cancers.
Methods: Next generation sequencing was performed on the DNA extracted samples, using the Illumina HiSeq2000/4000 on 315 cancer related genes and tumor mutation burden was reported.
Results: In 914 small cell lung cancer (SCLC) and 115 small cell of undefined primary (SCUP), there were similar and close rates of genetic alterations in lung lesions and distant metastatic foci in SCLC and SCUP. Also, the majority of tumors, both lung lesions and distant metastatic foci, did not carry a high tumor mutation burden. Multiple potentially targetable driver genes were identified. Despite common involvement of transmembrane signaling pathways and transcription machinery, other than TP53 and RB1, there was no considerable concurrent gene alteration.
Conclusion: This study showed similar genetic alteration and tumor mutation burden in the lung lesions and in distant metastatic foci. TP53 and RB1 were the frequently altered concurrently.