Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis

Andrea Espejo-Freire; Andrew Elliot; Andrew Rosenberg; Philippos Apolinario Costa; Priscila Barreto Coelho; Emily Jonczak; Gina D’Amato; Ty Subhawong; Junaid Arshad; Julio A. Diaz-Perez; W. Michael Korn; Matthew J. Oberley; Daniel Magee; Don Dizon; Margaret von Mehren; Moh'd M. Khushman; Atif Mahmoud Hussein; Kirsten Leu; Jonathan C. Trent

doi:10.20944/preprints202107.0068.v1

Submit preprint
How it Works
Instructions for Authors
Subject Areas
Advisory Board
screening preprints
About
Awards
Log in/Register

Instructions for Authors
Awards
About
FAQ
Submit Log in/Register

Share this article with

Create alert

Email:

Load new image

preprints.org > medicine and pharmacology > immunology and allergy > doi: 10.20944/preprints202107.0068.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis

Andrea Espejo-Freire

Andrew Elliot

Andrew Rosenberg

Philippos Apolinario Costa

Priscila Barreto Coelho

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.

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.

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

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

+ Respond to this comment

Not displayed online.

Importance: How significant is the paper to the field?

Outstanding/highlight paper

Significant contribution

Incremental contribution

No contribution

I am not qualified to judge

Soundness of evidence/arguments presented:

Conclusions well supported

Most conclusions supported (minor revision needed)

Incomplete evidence (major revision needed)

Hypothesis, unsupported conclusions, or proof-of-principle

I am not qualified to judge

Please leave your comment to this article below.

Mathematical equations can be typed in either LaTeX formats \\[ ... \\] or $$ ... $$, or MathML format <math> ... </math>. Try the LaTeX or MathML example.

Type equation:

Preview:

Copy equation into message below

Close menu

Please click a symbol to insert it into the message box below:

Please enter the link here:

Please enter a valid URL

Optionally, you can enter text that should appear as linked text:

Copy link into message below

Close menu

Please enter or paste the URL to the image here (please only use links to jpg/jpeg, png and gif images):

Please enter a valid URL

Copy image into message below

Close menu

Type author name or keywords to filter the list of references in this group (you can add a new citation under Bibliography):

No existing citations in Discussion Group

Wikify editor is a simple editor for wiki-style mark-up. It was written by MDPI for Sciforum in 2014. The rendering of the mark-up is based on Wiky.php with some tweaks. Rendering of mathematical equations is done with MathJax. Please send us a message for support or for reporting bugs.

Close menu

Please declare any conflicts of interest you may have with this paper, financial or otherwise.

I do not have a conflict of interest

I would like to declare a conflict of interest

Display my name on the website Send my name and email address to the authors

Captcha

Renew

I accept the following conditions:

Comments must follow the standards of professional discourse and should focus on the scientific content of the article. Insulting or offensive language, personal attacks and off-topic remarks will not be permitted. Comments must be written in English. Preprints reserves the right to remove comments without notice. Readers who post comments are obliged to declare any competing interests, financial or otherwise.

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)

* All users must log in before leaving a comment

what’s this?

Add a record of this review to Publons to track and showcase your reviewing expertise across the world’s journals.

Downloads 0

Comments 1

Metrics 0

Get PDF Cite Share 0

Bookmark BibSonomy Mendeley Reddit Delicious

Alerts

Notify me about updates to this article or when a peer-reviewed version is published.

Preprints.org is a free preprint server subsidized by MDPI in Basel, Switzerland.

MDPI Initiatives

SciProfiles
Sciforum
Encyclopedia
MDPI Books
Scilit
Proceedings
JAMS

Important links

How it Works
Advisory Board
FAQ
Friendly Journals
Instructions for Authors
About
Statistics

Choose the area that interest you and we will send you notifications of new preprints at your preferred frequency.

Disclaimer

We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.

RSS feed for

Preprints: The Multidisciplinary Preprint Platform

Paste the URL in your RSS reader:

https://www.preprints.org/rss

If you want to subscribe our website in subject-wide, you could find the URL by choosing in the following:

https://www.preprints.org/rss

Please note that by using ScienceDirect RSS feeds, you agree to our Terms of Use and Privacy Policy.