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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1515935
This article is part of the Research Topic Multi-omics Approaches to Identify Immune Profiles and Therapeutic Targets for Rare Cancers View all 3 articles

Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophages

Provisionally accepted
Tun Kiat Ko Tun Kiat Ko 1Zexi Guo Zexi Guo 1Bavani Kannan Bavani Kannan 1Boon Yee Lim Boon Yee Lim 1Jing Yi Lee Jing Yi Lee 1Zhimei Li Zhimei Li 1Elizabeth Chun Yong Lee Elizabeth Chun Yong Lee 1Bin Tean Teh Bin Tean Teh 2Jason Yongsheng Chan Jason Yongsheng Chan 1*
  • 1 Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore
  • 2 Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore

The final, formatted version of the article will be published soon.

    Recent epidemiological data suggests a rising incidence of breast angiosarcoma (AS-B) in the Western population, with over two-thirds related to irradiation or chronic lymphedema. However, unlike head and neck angiosarcoma (AS-HN), AS-B disease characteristics in Asia remain unclear. We examined clinical patterns of angiosarcoma patients (n = 176) seen in an Asian tertiary cancer centre from 1999 to 2021, and specifically investigated the molecular and immune features of AS-B in comparison to AS-HN. Data from whole genome sequencing (WGS), NanoString gene expression profiling and 10x Genomics Visium spatial transcriptomics were analyzed. Majority of cases were AS-HN (n = 104; 59.1%), while AS-B (n = 16, all females) accounted for 9.1% of the cases. The median age at diagnosis was 43 years (range, 26 to 74). Based on WGS, 4 of the 7 AS-B had non-synonymous somatic variants in 48 genes (range, 2 to 28 per case). These genes were functionally annotated and were enriched in cancer-related pathways such as regulation of cell differentiation, VEGFR and receptor tyrosine kinases signaling pathways. By NanoString gene expression profiling, AS-B, compared to AS-HN, were enriched for angiogenesis, notch signaling and metastasis-associated matrix remodeling pathways. Additionally, AS-B were enriched for macrophages and CD8+ T cells expression signatures. Similarly, Visium spatial transcriptomics showed that AS-B were enriched for macrophages and T-cells. In conclusion, in our AS-B cases, we observed a convergence of both mutational and expression signatures on angiogenic-related pathways. Thus, anti-angiogenic therapy could be an option to treat AS-B.

    Keywords: Sarcoma, next generation sequencing, Immunotherapy, tumor-infiltrating macrophages, immune-oncology

    Received: 23 Oct 2024; Accepted: 19 Dec 2024.

    Copyright: © 2024 Ko, Guo, Kannan, Lim, Lee, Li, Lee, Teh and Chan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jason Yongsheng Chan, Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.