Abstract 4740: Molecular profiling of adenoid cystic carcinomas

Abstract

Abstract Introduction: Adenoid cystic carcinomas (AdCC) are uncommon malignant neoplasm that can occur in different locations throughout the body. These tumors are typically characterized by the presence of MYB:NFIB or MYBL1:NFIB fusion, but not in every case. Methods: We analyzed 107 adenoid cystic carcinomas from various primary sites that were genetically profiled using a large NGS panel (592) genes in genomic DNA and whole transcriptome sequencing. Immunohistochemical staining was performed for PD-L1. Results: The primary sites included salivary gland (60), lung (15), sino-nasal passages (10), oral cavity (9) breast (5), head, face or neck or other sites (5), skin (1), vulva (1), and unknown primary site (1). Fusions were detected in 87 cases (81%). The two fusions known to be associated with AdCC, MYB:NFIB and MYBL1:NFIB, were detected in 67 specimens (56 MYB:NFIB, 11 MYBL1:NFIB). In addition several fusions of uncertain significance involving these genes were detected (each found in one sample): MYBL1:SGK3, CD274:NFIB, NFIB:AHI1, NFIB:LINC00271 and TOP2B:MYBL1. No fusions were detected in 20 AdCC; the most common primary sites being salivary glands (14) and lung (4). The most common mutations detected in genomic DNA from these specimens involved NOTCH1 (5 cases), KDM6A (4 cases) ARID1A and TP53 (3 cases each). Two lung primaries were PD-L1 positive, low expression. No pathogenic mutations were detected in 3 cases: 2 salivary gland tumors and 1 oral cavity tumor. In cases with MYBL1:NFIB fusion, the gene expression of MYB is in the lower 20th percentile (relative to the entire cohort) while MYBL1 expression is in the upper 80th percentile. Conversely in cases with the MYB:NFIB fusions, MYB expression is ectopic resulting in expression in the upper 80th percentile while MYLB1 in the lower 20th percentile. Conclusion: We detected a classic MYB:NFIB or MYBL1:NFIB fusion in 67 of 107 adenoid cystic carcinomas profiled in this study. There is a strong pattern linking the presence or absence of fusions with the expression of MYB and MYBL1. Thus, fusions are driving high expression of either MYB or MYBL1, but the gene not involved in the fusion shows evidence of reduced expression. We hypothesize that a negative feedback mechanism may result in reduced expression of the other MYB-family gene to maintain homeostasis. From the treatment perspective, rare primary lung AdCC are amenable for I-O therapy based on expression of PD-L1. Citation Format: Michelle Ellis, Jeff Swensen, Phillip Stafford, Zoran Gatalica. Molecular profiling of adenoid cystic carcinomas [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 4740.