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

doi:10.4172/2157-2518.1000328

Omid S Tehrani, Vincent A Miller + Show 6 more

Open Access

https://doi.org/10.4172/2157-2518.1000328

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Abstract

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.

Highlights

Neuroendocrine tumors are a wide array of different neoplasms arising from endocrine and nervous system origin
Samples were diagnosed by local pathologist and slides were submitted for hybrid capture based comprehensive genomic profiling (CGP) to Foundation Medicine (Cambridge, MA)
One hundred fifteen (115) samples were categorized as small cell carcinoma of undefined primary (SCUP)

Summary

Introduction

Neuroendocrine tumors are a wide array of different neoplasms arising from endocrine and nervous system origin They commonly express chromogranin A, synaptophysin (p38), neural adhesion molecule (CD56), neuron-specific enolase, or neurofilament. Small cell poorly differentiated neuroendocrine carcinomas are small round blue cells with rapid proliferation rate, lack of structural formation, and poor differentiation. These cancers are aggressive, invade and metastasize early, respond to chemotherapy and radiation, and relapse almost universally. The most common type is the small cell lung cancer (SCLC), counting for 15% of lung cancers with higher incidence among older males with smoking history [1-6] They can arise in many different organs and can be present in other cancers as well. Presence of a component of small cell neuroendocrine neoplasm in other tumors is associated with poor prognosis [7-9]

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