Angiosarcoma (ANGS)

Overview

Angiosarcoma is a malignant vascular neoplasm classified under soft tissue sarcomas in the OncoTree hierarchy (parent: SOFT_TISSUE). It can arise sporadically or as a radiation-associated (RT) sarcoma, most commonly in the breast/chest wall following prior radiation therapy for breast carcinoma.

Cohorts in the corpus

Recurrent alterations

  • MYC amplification in 75% of RT-AS, exclusively in breast/chest wall cases (87% of 38 breast cases); 13% in sporadic AS PMID:37350195.
  • FLT4 alterations (mostly amplification) in 16% of RT-AS vs 8% sporadic AS PMID:37350195.
  • CRKL amplification in 14% of RT-AS vs 9% sporadic AS PMID:37350195.
  • HRAS hotspot missense mutations (A59T, Q61R/L) in 14% of RT-AS vs 2% sporadic AS PMID:37350195.
  • KMT2D truncating/missense mutations in 11% of RT-AS vs 1% sporadic AS PMID:37350195.
  • TP53 alterations depleted in RT-AS (9%) relative to sporadic AS (23%) PMID:37350195.
  • KDR alterations depleted in RT-AS (11%) vs sporadic AS (24%) PMID:37350195.
  • CDKN2A/CDKN2B deletions nearly absent in RT-AS (2%) compared to other RT-sarcoma histotypes (29-92%) PMID:37350195.
  • RT-AS harbored the lowest fraction of genome altered (FGA, 9%) among all RT-sarcoma histotypes (P < 0.0001) PMID:37350195.

Subtypes

  • Radiation-associated angiosarcoma (RT-AS): Genomically distinct from sporadic AS, with enrichment of MYC, FLT4, CRKL, HRAS, KMT2D alterations and depletion of TP53, KDR, ATM, ATRX alterations. MYC-amplified RT-AS had significantly shorter latency from radiation to diagnosis (P = 0.0083) PMID:37350195.
  • Sporadic angiosarcoma: Enriched for TP53 (23%), KDR (24%), ATM (10%), and ATRX (7%) alterations relative to RT-AS PMID:37350195.

Therapeutic landscape

  • Both primary and RT-AS are treated with taxane-based chemotherapeutic regimens PMID:37350195.
  • The stress-activated MAPK cascade (CRKL, FLT4, HRAS, MYC) and VEGF/VEGFR signaling (FLT4, HRAS, KDR) pathways represent potential histotype-dependent therapeutic targets in RT-AS PMID:37350195.

Sources

  • PMID:37350195 — Dermawan JK et al., J Pathol 2023. Comparative genomic analysis of 82 RT-sarcomas including 44 RT-angiosarcomas.

This page was processed by crosslinker on 2026-05-04.