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- Title
Multiomic analysis and immunoprofiling reveal distinct subtypes of human angiosarcoma.
- Authors
Jason Yongsheng Chan; Jing Quan Lim; Joe Yeong; Ravi, Vinod; Guan, Peiyong; Boot, Arnoud; Timothy Kwang Yong Tay; Selvarajan, Sathiyamoorthy; Md Nasir, Nur Diyana; Loh, Jie Hua; Ong, Choon Kiat; Huang, Dachuan; Jing Tan; Zhimei Li; Cedric Chuan-Young Ng; Thuan Tong Tan; Masuzawa, Mikio; Ken Wing-Kin Sung; Farid, Mohamad; Richard Hong Hui Quek
- Abstract
Angiosarcomas are rare, clinically aggressive tumors with limited treatment options and a dismal prognosis. We analyzed angiosarcomas from 68 patients, integrating information from multiomic sequencing, NanoString immuno-oncology profiling, and multiplex immunohistochemistry and immunofluorescence for tumor-infiltrating immune cells. Through whole-genome sequencing (n = 18), 50% of the cutaneous head and neck angiosarcomas exhibited higher tumor mutation burden (TMB) and UV mutational signatures; others were mutationally quiet and non-UV driven. NanoString profiling revealed 3 distinct patient clusters represented by lack (clusters 1 and 2) or enrichment (cluster 3) of immune-related signaling and immune cells. Neutrophils (CD15+), macrophages (CD68+), cytotoxic T cells (CD8+), Tregs (FOXP3+), and PD-L1+ cells were enriched in cluster 3 relative to clusters 2 and 1. Likewise, tumor inflammation signature (TIS) scores were highest in cluster 3 (7.54 vs. 6.71 vs. 5.75, respectively; P < 0.0001). Head and neck angiosarcomas were predominant in clusters 1 and 3, providing the rationale for checkpoint immunotherapy, especially in the latter subgroup with both high TMB and TIS scores. Cluster 2 was enriched for secondary angiosarcomas and exhibited higher expression of DNMT1, BRD3/4, MYC, HRAS, and PDGFRB, in keeping with the upregulation of epigenetic and oncogenic signaling pathways amenable to targeted therapies. Molecular and immunological dissection of angiosarcomas may provide insights into opportunities for precision medicine.
- Subjects
ANGIOSARCOMA; CYTOTOXIC T cells; NUCLEOTIDE sequencing; CELL communication; IMMUNOFLUORESCENCE; TUMOR treatment; CELL lines; COMPARATIVE studies; INFLAMMATION; RESEARCH methodology; MEDICAL cooperation; PROTEINS; RESEARCH; SARCOMA; EVALUATION research
- Publication
Journal of Clinical Investigation, 2020, Vol 130, Issue 11, p5833
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI139080