Comprehensive Genomic Profiling and Precision Pathology for Clinically Advanced Salivary Gland Myoepithelial Carcinoma

Abstract

Myoepithelial carcinomas of salivary glands (MyC) are generally low-grade malignancies that can arise de novo or in the background of a pre-existing pleomorphic adenoma (CPA). However, on occasion, MyC can present or progress into inoperable locally advanced and/or metastatic disease. DNA was extracted from 40 microns of FFPE sections from 24 cases of relapsed, refractory and metastatic MyC. Comprehensive genomic profiling (CGP) was performed using a hybrid-capture, adaptor ligation-based next-generation sequencing assay. Tumor mutational burden (TMB) was calculated from a minimum of 1.11 Mb of sequenced DNA and reported as mutations/Mb. The results were analyzed for all classes of genomic alterations (GA), including base substitutions (sub), insertions and deletions (short variants), fusions, and copy number changes including amplifications (amp) and homozygous deletions. At the time of CGP, 10 (42%) MyC were stage III and 14 (58%) were stage IV. Of 22 cases where the primary site was known, 16 (73%) arose in the parotid, 1 (5%) in the submandibular SG, and 5 (22%) from accessory SG.Tabled 1Abstract 247MyC cases24Genomic alterations (GA)/case2.3Clinically Relevant GA (CRGA)RICTOR amp & PIK3CA sub (21% each) PTCH1 & PDGFRB sub (8 % each) NF1 & BRCA2 sub (4% each)Non-actionable GACDKN2A loss (25%) CDKN2B & HRAS sub (21% each) TERT, MYC, TP53 & NOTCH1 subs (13% each)TMB > 20 Mut/Mb2 (8%)TMB < 10 Mut/Mb22 *(92%)* No cases of ERBB2 GA and no cases of MSI-high status. Open table in a new tab * No cases of ERBB2 GA and no cases of MSI-high status. Clinically advanced MyC are similar to the usually less aggressive SG tumors, adenoid cystic, and acinic cell carcinomas in having a low frequency of GA, a low TP53 mutation frequency, low TMB, and general paucity of CRGA when compared to the usually more aggressive adenocarcinomas which may feature targetable driver alterations in ERBB2 and other pathways. However, the findings of potentially targetable alterations in RICTOR, PTCH1, NF1, and BRCA2 and the presence of high TMB, albeit in a relatively small percentage of MyC cases, encourage the continued use of CGP.