Abstract LB-310: Whole-exome sequencing reveals genetic underpinnings of salivary adenoid cystic carcinoma and tongue carcinoma in Chinese population

Abstract

Abstract Background: Salivary adenoid cystic carcinoma (ACC) and oral tongue squamous cell carcinoma (OTSCC) are rare malignancies with low incidence and dismal prognosis. The molecular underpinnings of these remain poorly understood, particularly in Asian population. Methods: Through a whole-exome sequencing analysis of 13 OTSCC and 30 ACC patients, a systematic overview of the mutational features in single-nucleotide variations, copy number variations and chromosomal variations were illustrated. Results: In addition to the well-characterized alterations previously reported in Caucasian patients, such as TP53 mutations (11/13, 84.6%) in OTSCC and MYB-NFIB fusion in ACC (11/30, 36.7%), we also observed several novel genetic changes, including FOXP1-TEX261 fusion (1/13, 7.7%) and MYB-FMO5 fusion (1/30, 3.3%) in OTSCC and ACC respectively, which might play a role in facilitating tumor progression. The data exhibited promising translational value as numerous actionable genes were identified with mutations. 76.9% OTSCC and 20% salivary ACC harbored at least one alteration in actionable genes, mutations in CDKN2A (4/13, 30.8%), NTRK3 (3/13, 23.1%) in OTSCC and FGFR2 (2/30, 6.7%), BRAF (2/30, 6.7%) in salivary gland ACC, suggesting targeted immunotherapy might be an effective intervention. Instead of MYB-independent NFIB fusions previously reported in ACC, only NFIB-independent MYB fusions were found in our cohort, indicating that alterations in NFIB rather than MYB might be essential to ACC tumorigenesis. Conclusions: This study reveals the genetic underpinnings of two rare malignancies in Chinese population, illustrating consistent mutational features with published literature as well as demonstrating several distinct genetic alterations, warranting further investigations. Citation Format: Ning Li, Shuhang Wang, Yue Yu, Yuan Fang, Huiyao Huang, Dawei Wu, Hong Fang, Chao Sun, Anqi Yu, Qi Fan, Shi-Yuan Cheng. Whole-exome sequencing reveals genetic underpinnings of salivary adenoid cystic carcinoma and tongue carcinoma in Chinese population [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-310.