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Uveal melanoma prognoses vary depending on genomic subset
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Four molecularly distinct subtypes of uveal melanomas have been identified, two with poorer prognosis and two with better prognosis, according to a study.
In a multiplatform analysis of 80 uveal melanomas, an international team of researchers used DNA sequencing to identify complex alterations in BAP1 that were not previously identified using standard algorithms.
Two subsets of the poorer prognosis tumor group, monosomy 3 (M3-UM), were found to have similar BAP1 alterations but different copy number alterations, RNA expression and cellular pathway activity. Two subsets of better prognosis tumor group, disomy 3 (D3-UM), were distinguished by somatic copy number changes and DNA methylation profiles. BAP1 alterations were observed in 85% of the M3-UM subgroups.
“Our integrated, multidimensional molecular and computational investigation into UM provides insights that have mechanistic, prognostic and therapeutic implications,” the researchers wrote. – by Rebecca L. Forand
Disclosure: See the study for a full list of authors’ financial disclosures.
Perspective
Back to TopHans E. Grossniklaus, MD, MBA
In this Rare Tumor Project of The Cancer Genome Atlas (TCGA), the authors performed a global and integrated molecular characterization of 80 primary uveal melanomas. The analyses included chromosome number variations (CNVs), DNA, mRNA, lncRNA and miRNA sequencing, protein expression and DNA methylation status. The data were analyzed using bioinformatic platforms.
There were four molecularly distinct groups of uveal melanoma (UM) identified. Going from best to worst prognosis for metastasis, group 1 exhibited disomy 3 (D3), EIF1AX gene alternations, specific CNVs and a specific DNA methylation pattern; group 2 exhibited D3, SF3B1 gene alternations, specific CNVs and specific DNA methylation patterns; group 3 exhibited monosomy 3, BAP1 alterations, specific CNVs and a specific DNA methylation pattern, and group 4 exhibited M3, BAP1 alterations, specific CNVs and a DNA methylation pattern similar to group 3. Additionally, a subset of the M3 poor prognosis UMs contained a T cell/macrophage infiltrate with associated upregulated chemokines and highly expressed IDO1/TIGIT (T cell checkpoint inhibitors) mRNAs.
Currently there are clinical trials targeting IDO1/TIGIT. This comprehensive molecular analysis of UM may lead to better therapies for primary and metastatic UM.
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Roberts AG, et al. Cancer Cell; 2017;doi:10.1016/j.ccell.2017.07.003.
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