Background: The human retinoblastoma susceptibility gene (RB1) is a tumor-suppressor gene mutated at different frequencies in many different cancers. The aim of the present study was to investigate the distribution of overall RB1 mutation and different mutation types in a range of Chinese patients with solid tumors.
Methods: We investigated RB1 mutations in formalin-fixed, paraffin-embedded (FFPE) tissues of cancer patients who underwent next-generation sequencing (NGS) at 3DMed Clinical Laboratory Inc from January 1, 2017 to April 15, 2020.
Results: Genomic alterations in RB1 were identified in 1,712 (7.6%) of 22,432 patients with more than 20 different cancer entities (58% males and 42% females, median age: 60 years). RB1 mutations occurred most frequently in small-cell lung cancer (SCLC; 138/165, 83.6%), followed by neuroendocrine neoplasms (40/170, 23.5%), bladder cancer (40/209, 19.1%), hepatocellular carcinoma (233/1,649, 14.1%), sarcomas (71/554, 12.8%), and esophageal cancer (32/293, 10.9%). Of these 1,712 patients, 185 (10.8%) had germline RB1 mutations. When stratified by mutational type, 1,258 (5.6%) had single-nucleotide variants (SNVs), 59 (0.3%) had fusions, and 210 (0.9%) had RB1 loss.
Conclusions: Our findings indicate that RB1 alterations are widely distributed in solid cancers of many different histotypes in China, with specific mutations differing largely among different tumor types. The present study provides a comprehensive landscape of RB1 mutations in Chinese solid tumor patient and suggests a novel therapeutic target for cancer treatment.
Keywords: Retinoblastoma susceptibility gene (RB1); cyclin-dependent kinase 4/6 inhibitor; next-generation sequencing (NGS); resistance; solid tumor.
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