Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis

Version 1 : Received: 1 July 2021 / Approved: 2 July 2021 / Online: 2 July 2021 (15:43:54 CEST)

A peer-reviewed article of this Preprint also exists.

Espejo-Freire, A.P.; Elliott, A.; Rosenberg, A.; Costa, P.A.; Barreto-Coelho, P.; Jonczak, E.; D’Amato, G.; Subhawong, T.; Arshad, J.; Diaz-Perez, J.A.; Korn, W.M.; Oberley, M.J.; Magee, D.; Dizon, D.; von Mehren, M.; Khushman, M.M.; Hussein, A.M.; Leu, K.; Trent, J.C. Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis. Cancers 2021, 13, 4816. Espejo-Freire, A.P.; Elliott, A.; Rosenberg, A.; Costa, P.A.; Barreto-Coelho, P.; Jonczak, E.; D’Amato, G.; Subhawong, T.; Arshad, J.; Diaz-Perez, J.A.; Korn, W.M.; Oberley, M.J.; Magee, D.; Dizon, D.; von Mehren, M.; Khushman, M.M.; Hussein, A.M.; Leu, K.; Trent, J.C. Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis. Cancers 2021, 13, 4816.

Journal reference: Cancers 2021, 13, 4816
DOI: 10.3390/cancers13194816

Abstract

We performed a comprehensive analysis of angiosarcoma (AS) genomic biomarkers and their associations with the site of origin. We aimed to describe the genomic landscape of AS in a cohort of 143 cases of AS profiled by Caris Life Sciences. Data of Next Generation Sequencing (NGS) with a 592 gene panel was available for the entire cohort. Fifty-three cases had data of Whole Exome Sequencing (WES) which we used to study the microenvironment phenotype. Immuno-therapy (IO) response biomarkers: Tumor Mutation Burden (TMB), Microsatellite Instability (MSI) and PD-L1 status were included. IO-response markers were present in 36.4% of the cohort and in 65% of head and neck AS (H/N-AS) (p<0.0001). H/N-AS cases had predominantly muta-tions in TP53 (50.0%, p=0.0004), POT1 (40.5%, p<0.0001) and ARID1A (33.3%, p=0.5875). In breast AS, leading alterations were MYC amplification (63.3%, p<0.0001), HRAS (16.1%, p=0.0377), and PI3KCA (16.1%, p=0.2352). A microenvironment with a high immune signature, associated with better response to IO, was present in 13% of the cases. This signature was evenly distributed among different primary sites. We found that the molecular biology for AS varies significantly according to the primary site. Our findings can facilitate the design and optimiza-tion of therapeutic strategies for AS to overcome resistance to IO and targeted therapies.

Keywords

Angiosarcoma; biomarkers; tumor microenvironment; immunotherapy, next generation sequencing, whole transcriptome sequencing.

Comments (1)

Comment 1
Received: 14 July 2021
Commenter: Ulrich Pfeffer
The commenter has declared there is no conflict of interests.
Comment: Very interesting article, my compliments.
I have just a few comments:
- You describe differences in the mutational landscape and in the TMB according to the anatomical site in which the AS occurs. Do you have any explanation for this observation considering that the etiological agent, radiation, is the same in all cases?
- It would be interesting to also look at mutational signatures. Are they also different according to site?
- Is MYC overexpressed in cases with amplification of this locus?

sincerely,

U. Pfeffer
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