Repeatedly next-generation sequencing during treatment follow-up of patients with small cell lung cancer.

Abstract

Somatic alterations in tumors are a frequent occurrence. In small cell lung cancer (SCLC), these include mutations in the tumor suppressors TP53 and retinoblastoma (RB1). We used next generation sequencing (NGS) to study specific genetic variants and compare genetic and clinicopathological features of SCLC with healthy control genome. Ten SCLC patients receiving standard chemotherapy, between 2018 and 2019, from the First Hospital of Jilin University were included in this study. Prior patient treatment, NGS was performed using DNA isolated from blood plasma. New NGS analyses were performed after 2 and 4 treatment cycles. Four patients presented with different metastases at diagnosis. Overall, most genes tested presented missense or frameshift variants. TP53, RB1, CREBBP, FAT1 genes presented gain of stop codons. At the single-gene level, the most frequently altered genes were TP53 (8/10 patients, 80%) and RB1 (4/10 patients, 40%), followed by bromodomain containing 4 (BRD4), CREBBP, FAT1, FMS-like tyrosine kinase 3 (FLT3), KDR, poly ADP-ribose polymerase (PARP1), PIK3R2, ROS1, and splicing factor 3b subunit 1 (SF3B1) (2/10 patients, 20%). We identified 5 genes, which have not been previously reported to bear mutations in the context of SCLC. These genes include BRD4, PARP1, FLT3, KDR, and SF3B1. We observed that among the studied individuals, patients with a high number of genetic events, and in which such mutations were not eradicated after treatment, showed a worse prognosis. There has not yet been given enough attention to the above-mentioned genes in SCLC, which will have great clinical prospects for treatment.