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Review
. 2025 Apr;19(4):965-983.
doi: 10.1002/1878-0261.13744. Epub 2024 Oct 5.

Genomic landscape and preclinical models of angiosarcoma

Annaleigh Benton  1   2 , Bozhi Liu  1   2 , Lauren E Gartenhaus  1   2 , Jason A Hanna  1   2
Affiliations
Review

Genomic landscape and preclinical models of angiosarcoma

Annaleigh Benton et al. Mol Oncol. 2025 Apr.

Abstract

Angiosarcoma is a cancer that develops in blood or lymphatic vessels that presents a significant clinical challenge due to its rarity and aggressive features. Clinical outcomes have not improved in decades, highlighting a need for innovative therapeutic strategies to treat the disease. Genetically, angiosarcomas exhibit high heterogeneity and complexity with many recurrent mutations. However, recent studies have identified some common features within anatomic and molecular subgroups. To identify potential therapeutic vulnerabilities, it is essential to understand and integrate the mutational landscape of angiosarcoma with the models that exist to study the disease. In this review, we will summarize the insights gained from reported genomic alterations in molecular and anatomic subtypes of angiosarcoma, discuss several potential actionable targets, and highlight the preclinical disease models available in the field.

Keywords: angiosarcoma; genomics; rare cancer; sarcoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Genetic landscape of overall angiosarcoma patients. Stacked bar graph with the top 12 most frequent genomic alterations found in angiosarcoma. Genes are arranged according to overall alteration rate (right y‐axis, gray line) with the total number of alterations found for each gene (left y‐axis, stacked bar graph). The number of alterations and total number of samples sequenced for each gene are: TP53 (144/659), MYC (143/659), KDR (88/661), POT1 (53/638), ATRX (46/574), PIK3CA (53/665), FLT4 (52/658), PTPRB (37/470), RAS (52/665 with HRAS (28/665), NRAS (16/665), and KRAS (8/665)), ARID1A (38/539), CRKL (42/637), and ATM (32/640).
Fig. 2
Fig. 2
Genetic landscape of head and neck angiosarcoma. (A) Stacked bar graph with the top 10 head and neck angiosarcoma (HN‐AS) genomic mutations from seven independent studies. Genes are arranged by alteration rate (right axis, gray line) with total number of alterations found for each gene (left axis, stacked bar graph). The number of alterations and total number of samples sequenced for each gene are: TP53 (49/142), POT1 (31/143), CRKL (14/141), ARID1A (11/116), FLT4 (13/141), LRP1B (13/143), ATRX (10/122), MYC (10/141), SETD2 (10/143), and ATM (8/143). (B) Chord diagram generated by PlotAPI [27] of co‐occurring alterations involving TP53, POT1, CRKL, and FLT4 observed in two or more HN‐AS patients.
Fig. 3
Fig. 3
Genetic landscape of primary breast angiosarcoma. (A). Oncoprint with genomic variants and copy number changes in frequently altered genes in primary breast angiosarcoma (AS). ‘Other’ includes non‐frameshift indel, in‐frame deletion, multi‐hit mutations, and biallelic inactivation of tumor suppressor genes. (B) Chord diagram generated by PlotAPI [27] of frequent co‐occurring alterations found in two or more primary breast AS patients.
Fig. 4
Fig. 4
Potential targeted therapies for angiosarcoma. Altered pathways and potential therapeutic opportunities in angiosarcoma.
See this image and copyright information in PMC

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