Posted: August 14, 2017

View the TCGA study of uveal melanoma here

TCGA Study of Uveal Melanoma Reveals Prognostic Subtypes

In a comprehensive, multiplatform analysis of 80 primary uveal melanoma (UM) tumors, researchers of The Cancer Genome Atlas Research Network identified and characterized four distinct subtypes that have unique genomic aberrations, gene expression features, and patient outcomes. Cancers of the uvea, the pigmented middle layer of the eye, are relatively rare and have not been previously well-studied. Up to 50% of UM patients develop metastatic disease, for which there are no effective therapies. This study, published in Cancer Cell on August 14, 2017, suggests that the four subtypes uncovered, each with unique molecular pathway changes and associated clinical prognoses, may require different therapeutic strategies.

The researchers deployed a range of sequencing technologies and novel analytical approaches to characterize molecularly and clinically distinct subtypes of UM. Notably, using DNA-seq and RNA-seq reassembly, they identified multiple novel and complex alterations of the BAP1 gene that otherwise would not have been found. These BAP1 alterations, along with global DNA methylation profiling, can distinguish the previously known disomy 3 (D3-UM) and monosomy 3 (M3-UM) subtypes of UM, which carry more and less favorable prognoses, respectively. Within M3-UM, the investigators found that genomic aberrations, gene expression characteristics, and immune profiles further divide the group into distinct clinical outcomes. The researchers also refined the D3-UM subtype: they identified mutually exclusive EIF1AX- and SRSF2/SF3B1-mutant tumors with distinct somatic copy number alterations and DNA methylation profiles that may contribute to different prognoses. These subtypes may aid in stratifying patients based on the aggressiveness of their disease. Overall, this study expanded our basic understanding of a rare, deadly disease and revealed novel genomic characteristics that may guide the development and application of tailored clinical strategies for UM subtypes in the future. TCGA is a collaboration jointly supported and managed by the National Cancer Institute and the National Human Genome Research Institute, both parts of the National Institutes of Health.