TY - JOUR
T1 - Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome
AU - Kenawy, Nihal
AU - Kalirai, Helen
AU - Sacco, Joseph J.
AU - Lake, Sarah L.
AU - Heegaard, Steffen
AU - Larsen, Ann Cathrine
AU - Finger, Paul T.
AU - Milman, Tatyana
AU - Chin, Kimberly
AU - Mosci, Carlo
AU - Lanza, Francesco
AU - Moulin, Alexandre
AU - Schmitt, Caroline A.
AU - Caujolle, Jean Pierre
AU - Maschi, Célia
AU - Marinkovic, Marina
AU - Taktak, Azzam F.
AU - Heimann, Heinrich
AU - Damato, Bertil E.
AU - Coupland, Sarah E.
N1 - Publisher Copyright:
© 2019 The Authors. Pigment Cell & Melanoma Research Published by John Wiley & Sons Ltd.
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
KW - BRAF/NRAS mutation
KW - allele-specific copy number
KW - conjunctival melanoma
KW - copy number alteration
KW - metastasis
UR - http://www.scopus.com/inward/record.url?scp=85067555018&partnerID=8YFLogxK
U2 - 10.1111/pcmr.12767
DO - 10.1111/pcmr.12767
M3 - Article
C2 - 30672666
AN - SCOPUS:85067555018
SN - 1755-1471
VL - 32
SP - 564
EP - 575
JO - Pigment Cell and Melanoma Research
JF - Pigment Cell and Melanoma Research
IS - 4
ER -