Abstract 2229: Landscape of RB1 alterations in 22,432 Chinese solid tumor patients

Abstract

Abstract Background: The retinoblastoma susceptibility gene (RB1) is one of tumor suppressor genes. This gene is mutated at variable frequencies in a variety of other human cancers. Cancer genome sequencing revealed that most types of cancer with RB1 mutation were retinoblastomas, osteosarcomas, and small-cell lung cancers, and its mutation was also found in other cancer types with a lower frequency, for instance, prostate cancer, breast cancer and etc. RB1 protein plays a prominent role in a variety of molecular processes related to DNA including gene transcription, DNA replication, DNA repair, and mitosis. However, no comprehensive status of RB1 alterations in Chinese populations with solid tumor has been reported yet. Methods: The Formalin-Fixed Paraffin-Embedded (FFPE) tissues from solid tumor patients who have underwent next-generation sequencing (NGS) from January 01, 2017 to April 15, 2020 in 3DMed Clinical Laboratory Inc. (a College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory) were analyzed. The diagnosis of the tissues was confirmed by hematoxylin and eosin (H&E) staining. The single nucleotide variants (SNVs), copy number variants (CNVs) and gene rearrangements data of these patients were analyzed. Results: Of 22,432 Chinese solid tumor patients with more than 20 tumor types (58% males and 42% females, with median age was 60 years), genomic alterations in RB1 were observed in 1712 (7.6%) patients. RB1 mutations occurred most frequently in small cell lung cancer (138/165, 83.6%), followed by neuroendocrine neoplasms (42/170, 24.7%), sarcoma (127/554, 22.9%), biliary tract cancer (40/209, 19.1%), head and neck cancer (4/22, 18.2%), and liver cancer (232/1649, 14.1%). And (185/1712, 10.8%) patients were detected with germline RB1 mutation. When stratified by the mutational types, 1,443 (6.4%) patients were with SNVs, 59 (0.3%) with fusions, and 210 (0.9%) with loss in RB1 gene. Conclusion: Our results suggested RB1 alteration was widely occurred in solid tumor patients in China, and specific alteration rates differed largely between tumor types. Our study also suggested usage of NGS in the need for individualized characterization of cancers and further investigations are warranted for the cancer treatment upon molecular profiling in the clinical therapeutic setting. Citation Format: Nan Wang, Xueke She, Depei Huang, Xudong Shen, Hushan Zhang, Gang Ji. Landscape of RB1 alterations in 22,432 Chinese solid tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2229.