Uveal Melanoma / UVM (TCGA)

Overview

UVM is the TCGA cohort identifier for uveal melanoma. The corresponding OncoTree code is UM (Uveal Melanoma). Uveal melanoma is biologically distinct from cutaneous melanoma: it is driven primarily by GNAQ/GNA11 mutations, has very low mutation burden (no UV signature), frequently metastasizes to the liver, and has an extremely poor prognosis upon metastasis. UVM has distinctive arm-level copy-number patterns including chromosome 3 monosomy and 8q amplification.

Cohorts in the corpus

  • TCGA UVM cohort: included as one of 33 cancer types in the MC3 pan-cancer mutation-calling project, the pan-cancer fusion landscape study, and the pan-cancer aneuploidy study; subset of the PanCancer Atlas (uvm_tcga_pan_can_atlas_2018).

Recurrent alterations

  • MC3 pan-cancer mutation-calling project identified UVM as showing large sample-to-sample variability in mutations per sample alongside KICH, PAAD, and THYM PMID:29596782.
  • Pan-cancer fusion study (9,624 TCGA samples) found UVM has a median of 0 fusions per sample PMID:29617662.
  • Pan-cancer aneuploidy study found UVM is an exception to the positive aneuploidy–mutation-rate correlation (driven by its MSI/POLE-free but low-mutation character); UVM clusters in the neural-lineage arm-level group with GBM and LGG (melanoma subgroup); chromosome 3 monosomy and 8q gain are defining SCNA features PMID:29622463.

Subtypes

  • Monosomy 3 / BAP1-mutant: high metastatic risk.
  • Disomy 3 / BAP1-wild-type: lower metastatic risk.
  • GNAQ and GNA11 Q209 hotspot mutations are nearly universal (~90% combined); EIF1AX, SF3B1, and BAP1 mutations further stratify prognosis.

Therapeutic landscape

No drug-specific findings for UVM reported in the current corpus; MEK inhibitors and liver-directed therapies are investigational.

Sources

  • PMID:29596782 — MC3 multi-center mutation calling (Ellrott et al., 2018)
  • PMID:29617662 — Pan-cancer fusion landscape (Gao et al., 2018)
  • PMID:29622463 — Pan-cancer aneuploidy landscape (Taylor et al., 2018)

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