Angiosarcoma (AS) is a rare malignancy with a heterogeneous clinical presentation and genetic background. Different clinical AS subtypes can be envisaged, including: visceral, deep-seated soft tissue (ST), radiation induced (RT) and UV associated (UV) origin. To better understand their distinct biology and clinical outcome we investigated DNA methylation profiles, chromosomal stability and survival of these four subtypes.
After ethical approval, FFPE samples of AS from visceral, ST, RT and UV origin were collected from a nationwide search by the Dutch nationwide network and registry of histo- and cytopathology. DNA was extracted for methylation profiling with the Illumina Infinium MethylationEPIC array (German Cancer Research Center, Heidelberg, Germany). Quality control and unsupervised hierarchical clustering based on the 1% most varying methylation probes took place at Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. Copy number profiles were generated for chromosomal stability assessment. Anonymized clinical data were obtained from the Netherlands Cancer Registry.
DNA methylation profiling and unsupervised hierarchical clustering of 36 AS samples (6 visceral, 5 ST, 14 RT, 11 UV), revealed two main clusters (A and B) and four subclusters (Table). The different clusters corresponded with clinical origin, showing enrichment of UV cases in cluster A1 and RT cases in cluster A2. Cluster A showed significantly more chromosomal aberrations and better median overall survival compared to cluster B (22.2 vs 5.5 months, p = 0.046).Table:
1711P Cluster characteristics
|Subtype||7 UV||10 RT, 1 ST||4 ST, 3 Visceral||4 RT, 4 UV, 3 Visceral|
|Median survival (months, range)||22 (2-106)||23 (1-281)||4 (2-55)||7 (0-40)|
In this novel DNA methylation profiling study, we demonstrated for the first time four different AS clusters. These clusters strongly correlated with clinical origin, chromosomal stability and overall survival. Further research is warranted in a larger patient cohort to better define the clinical significance of the different clusters.
Clinical trial identification
Legal entity responsible for the study
HDKT (Honderdduizend Keer een Tientje).
I.M.E. Desar: Research grant / Funding (institution): Novartis. W.T. van der Graaf: Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Bayer. All other authors have declared no conflicts of interest.