Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis

Abstract

We performed a retrospective analysis of angiosarcoma (AS) genomic biomarkers and their associations with the site of origin in a cohort of 143 cases. Primary sites were head and neck (31%), breast (22%), extremity (11%), viscera (20%), skin at other locations (8%), and unknown (9%). All cases had Next Generation Sequencing (NGS) data with a 592 gene panel, and 53 cases had Whole Exome Sequencing (WES) data, which we used to study the microenvironment phenotype. The immunotherapy (IO) response biomarkers Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), and PD-L1 status were the most frequently encountered alteration, present in 36.4% of the cohort and 65% of head and neck AS (H/N-AS) (<i>p</i> < 0.0001). In H/N-AS, TMB-High was seen in 63.4% of cases (<i>p</i> < 0.0001) and PDL-1 positivity in 33% of cases. The most common genetic alterations were <i>TP53</i> (29%), <i>MYC</i> amplification (23%), <i>ARID1A</i> (17%), <i>POT1</i> (16%), and <i>ATRX</i> (13%). H/N-AS cases had predominantly mutations in <i>TP53</i> (50.0%, <i>p</i> = 0.0004), <i>POT1</i> (40.5%, <i>p</i> < 0.0001), and <i>ARID1A</i> (33.3%, <i>p</i> = 0.5875). In breast AS, leading alterations were <i>MYC</i> amplification (63.3%, <i>p</i> < 0.0001), <i>HRAS</i> (16.1%, <i>p</i> = 0.0377), and <i>PIK3CA</i> (16.1%, <i>p</i> = 0.2352). At other sites, conclusions are difficult to generate due to the small number of cases. A microenvironment with a high immune signature, previously associated with IO response, was evenly distributed in 13% of the cases at different primary sites. Our findings can facilitate the design and optimization of therapeutic strategies for AS.