Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis
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 N...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/19/4816 |
| _version_ | 1797516715473502208 |
|---|---|
| author | Andrea P. Espejo-Freire Andrew Elliott Andrew Rosenberg Philippos Apolinario Costa Priscila Barreto-Coelho Emily Jonczak Gina D’Amato Ty Subhawong Junaid Arshad Julio A. Diaz-Perez Wolfgang M. Korn Matthew J. Oberley Daniel Magee Don Dizon Margaret von Mehren Moh’d M. Khushman Atif Mahmoud Hussein Kirsten Leu Jonathan C. Trent |
| author_facet | Andrea P. Espejo-Freire Andrew Elliott Andrew Rosenberg Philippos Apolinario Costa Priscila Barreto-Coelho Emily Jonczak Gina D’Amato Ty Subhawong Junaid Arshad Julio A. Diaz-Perez Wolfgang M. Korn Matthew J. Oberley Daniel Magee Don Dizon Margaret von Mehren Moh’d M. Khushman Atif Mahmoud Hussein Kirsten Leu Jonathan C. Trent |
| author_sort | Andrea P. Espejo-Freire |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T07:04:43Z |
| format | Article |
| id | doaj.art-4f9d07b0251b4119becd26d25c7be9ce |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T07:04:43Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4f9d07b0251b4119becd26d25c7be9ce2023-11-22T15:52:46ZengMDPI AGCancers2072-66942021-09-011319481610.3390/cancers13194816Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker AnalysisAndrea P. Espejo-Freire0Andrew Elliott1Andrew Rosenberg2Philippos Apolinario Costa3Priscila Barreto-Coelho4Emily Jonczak5Gina D’Amato6Ty Subhawong7Junaid Arshad8Julio A. Diaz-Perez9Wolfgang M. Korn10Matthew J. Oberley11Daniel Magee12Don Dizon13Margaret von Mehren14Moh’d M. Khushman15Atif Mahmoud Hussein16Kirsten Leu17Jonathan C. Trent18Department of Medicine, Hematology & Oncology, Sylvester Comprehensive Cancer Center, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Clinical and Translational Research, Caris Life Sciences, Phoenix, AZ 85040, USADepartment of Pathology, Sylvester Comprehensive Cancer Center, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Medicine, Hematology & Oncology, Sylvester Comprehensive Cancer Center, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Medicine, Hematology & Oncology, Sylvester Comprehensive Cancer Center, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Medicine, Hematology & Oncology, Sylvester Comprehensive Cancer Center, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Medicine, Hematology & Oncology, Sylvester Comprehensive Cancer Center, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Radiology, Sylvester Comprehensive Cancer Center, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Medicine, Medical Oncology, The University of Arizona College of Medicine, University of Arizona Cancer Center, Tucson, AZ 85724, USADepartment of Pathology, Sylvester Comprehensive Cancer Center, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Medical Affairs, Caris Life Sciences, Phoenix, AZ 85040, USADepartment of Pathology and Genetics, Caris Life Sciences, Phoenix, AZ 85040, USADepartment of Cognitive Computing, Caris Life Sciences, Phoenix, AZ 85040, USADepartment of Medical Oncology and Gynecologic Medical Oncology, Lifespan Cancer Institute, Rode Island Hospital, Providence, RI 02903, USADepartment of Hematology & Oncology, Fox Chase Cancer Center, Temple Health, Philadelphia, PA 19111, USAO’Neal Comprehensive Cancer Center, Department of Medicine, Hematology & Oncology, The University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Hematology & Oncology, Memorial Health Care System, Memorial Cancer Institute, Hollywood, FL 33021, USAMedical Oncology, Nebraska Cancer Specialists, Omaha, NE 68114, USADepartment of Medicine, Hematology & Oncology, Sylvester Comprehensive Cancer Center, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami, FL 33136, USAWe 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.https://www.mdpi.com/2072-6694/13/19/4816Angiosarcomabiomarkerstumor microenvironmentimmunotherapynext-generation sequencingwhole transcriptome sequencing |
| spellingShingle | Andrea P. Espejo-Freire Andrew Elliott Andrew Rosenberg Philippos Apolinario Costa Priscila Barreto-Coelho Emily Jonczak Gina D’Amato Ty Subhawong Junaid Arshad Julio A. Diaz-Perez Wolfgang M. Korn Matthew J. Oberley Daniel Magee Don Dizon Margaret von Mehren Moh’d M. Khushman Atif Mahmoud Hussein Kirsten Leu Jonathan C. Trent Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis Cancers Angiosarcoma biomarkers tumor microenvironment immunotherapy next-generation sequencing whole transcriptome sequencing |
| title | Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis |
| title_full | Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis |
| title_fullStr | Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis |
| title_full_unstemmed | Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis |
| title_short | Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis |
| title_sort | genomic landscape of angiosarcoma a targeted and immunotherapy biomarker analysis |
| topic | Angiosarcoma biomarkers tumor microenvironment immunotherapy next-generation sequencing whole transcriptome sequencing |
| url | https://www.mdpi.com/2072-6694/13/19/4816 |
| work_keys_str_mv | AT andreapespejofreire genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT andrewelliott genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT andrewrosenberg genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT philipposapolinariocosta genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT priscilabarretocoelho genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT emilyjonczak genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT ginadamato genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT tysubhawong genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT junaidarshad genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT julioadiazperez genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT wolfgangmkorn genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT matthewjoberley genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT danielmagee genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT dondizon genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT margaretvonmehren genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT mohdmkhushman genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT atifmahmoudhussein genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT kirstenleu genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis AT jonathanctrent genomiclandscapeofangiosarcomaatargetedandimmunotherapybiomarkeranalysis |