Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome

Pigment Cell Melanoma Res. 2019 Jul;32(4):564-575. doi: 10.1111/pcmr.12767. Epub 2019 Feb 19.

Abstract

Relatively little is known about the genetic aberrations of conjunctival melanomas (CoM) and their correlation with clinical and histomorphological features as well as prognosis. The aim of this large collaborative multicenter study was to determine potential key biomarkers for metastatic risk and any druggable targets for high metastatic risk CoM. Using Affymetrix single nucleotide polymorphism genotyping arrays on 59 CoM, we detected frequent amplifications on chromosome (chr) 6p and deletions on 7q, and characterized mutation-specific copy number alterations. Deletions on chr 10q11.21-26.2, a region harboring the tumor suppressor genes, PDCD4, SUFU, NEURL1, PTEN, RASSF4, DMBT1, and C10orf90 and C10orf99, significantly correlated with metastasis (Fisher's exact, p ≤ 0.04), lymphatic invasion (Fisher's exact, p ≤ 0.02), increasing tumor thickness (Mann-Whitney, p ≤ 0.02), and BRAF mutation (Fisher's exact, p ≤ 0.05). This enhanced insight into CoM biology is a step toward identifying patients at risk of metastasis and potential therapeutic targets for systemic disease.

Keywords: BRAF/NRAS mutation; allele-specific copy number; conjunctival melanoma; copy number alteration; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Conjunctival Neoplasms / genetics*
  • Conjunctival Neoplasms / pathology
  • DNA Copy Number Variations / genetics*
  • DNA Mutational Analysis
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Karyotype
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Metastasis
  • Risk Factors
  • Treatment Outcome