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Tumor and Peripheral Immune Status in Soft Tissue Sarcoma: Implications for Immunotherapy
Article

Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis

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Department of Medicine, Hematology & Oncology, Sylvester Comprehensive Cancer Center, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
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Department of Clinical and Translational Research, Caris Life Sciences, Phoenix, AZ 85040, USA
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Department of Pathology, Sylvester Comprehensive Cancer Center, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
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Department of Radiology, Sylvester Comprehensive Cancer Center, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
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Department of Medicine, Medical Oncology, The University of Arizona College of Medicine, University of Arizona Cancer Center, Tucson, AZ 85724, USA
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Department of Medical Affairs, Caris Life Sciences, Phoenix, AZ 85040, USA
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Department of Pathology and Genetics, Caris Life Sciences, Phoenix, AZ 85040, USA
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Department of Cognitive Computing, Caris Life Sciences, Phoenix, AZ 85040, USA
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Department of Medical Oncology and Gynecologic Medical Oncology, Lifespan Cancer Institute, Rode Island Hospital, Providence, RI 02903, USA
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Department of Hematology & Oncology, Fox Chase Cancer Center, Temple Health, Philadelphia, PA 19111, USA
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O’Neal Comprehensive Cancer Center, Department of Medicine, Hematology & Oncology, The University of Alabama at Birmingham, Birmingham, AL 35233, USA
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Department of Hematology & Oncology, Memorial Health Care System, Memorial Cancer Institute, Hollywood, FL 33021, USA
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Medical Oncology, Nebraska Cancer Specialists, Omaha, NE 68114, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Joanna Szkandera and Dimosthenis Andreou
Cancers 2021, 13(19), 4816; https://doi.org/10.3390/cancers13194816
Received: 1 July 2021 / Revised: 15 September 2021 / Accepted: 18 September 2021 / Published: 26 September 2021
(This article belongs to the Special Issue Novel Therapeutic Considerations in Bone and Soft Tissue Sarcoma)
Angiosarcomas (AS) are rare, highly aggressive sarcomas with limited therapeutic options. Genomic sequencing techniques have identified recurrent genetic abnormalities. Nevertheless, the association of these findings with etiology, site of origin, prognosis, and therapeutic implications is not well understood. We analyzed Next Generation Sequencing (NGS) and Whole Transcriptome Sequencing (WTS) data in a cohort of 143 AS cases. We identified distinct genomic biology according to the AS primary site. Head and neck AS cases primarily have Immunotherapy (IO) response markers and mutations in TP53 and POT1. On the other hand, breast AS is enriched for cell cycle alterations, predominately MYC amplification. Additionally, a microenvironment with abundant immune cells is present in a minority of cases but distributed evenly among primary sites. Our findings can facilitate the design and optimization of therapeutic strategies for AS according to its biology at different primary sites.
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) (p < 0.0001). In H/N-AS, TMB-High was seen in 63.4% of cases (p < 0.0001) and PDL-1 positivity in 33% of cases. The most common genetic alterations were TP53 (29%), MYC amplification (23%), ARID1A (17%), POT1 (16%), and ATRX (13%). H/N-AS cases had predominantly mutations 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 PIK3CA (16.1%, p = 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. View Full-Text
Keywords: Angiosarcoma; biomarkers; tumor microenvironment; immunotherapy; next-generation sequencing; whole transcriptome sequencing Angiosarcoma; biomarkers; tumor microenvironment; immunotherapy; next-generation sequencing; whole transcriptome sequencing
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MDPI and ACS Style

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. https://doi.org/10.3390/cancers13194816

AMA Style

Espejo-Freire AP, Elliott A, Rosenberg A, Costa PA, Barreto-Coelho P, Jonczak E, D’Amato G, Subhawong T, Arshad J, Diaz-Perez JA, Korn WM, Oberley MJ, Magee D, Dizon D, von Mehren M, Khushman MM, Hussein AM, Leu K, Trent JC. Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis. Cancers. 2021; 13(19):4816. https://doi.org/10.3390/cancers13194816

Chicago/Turabian Style

Espejo-Freire, Andrea P., Andrew Elliott, Andrew Rosenberg, Philippos A. Costa, Priscila Barreto-Coelho, Emily Jonczak, Gina D’Amato, Ty Subhawong, Junaid Arshad, Julio A. Diaz-Perez, William M. Korn, Matthew J. Oberley, Daniel Magee, Don Dizon, Margaret von Mehren, Moh’d M. Khushman, Atif M. Hussein, Kirsten Leu, and Jonathan C. Trent 2021. "Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis" Cancers 13, no. 19: 4816. https://doi.org/10.3390/cancers13194816

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