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

Nihal Kenawy; Helen Kalirai; Joseph J Sacco; Sarah L Lake; Steffen Heegaard; Ann-Cathrine Larsen; Paul T Finger; Tatyana Milman; Kimberly Chin; Carlo Mosci; Francesco Lanza; Alexandre Moulin; Caroline A Schmitt; Jean Pierre Caujolle; Célia Maschi; Marina Marinkovic; Azzam F Taktak; Heinrich Heimann; Bertil E Damato; Sarah E Coupland

doi:10.1111/pcmr.12767

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

Nihal Kenawy, Helen Kalirai, Joseph J Sacco, Sarah L Lake, Steffen Heegaard, Ann-Cathrine Larsen, Paul T Finger, Tatyana Milman, Kimberly Chin, Carlo Mosci, Francesco Lanza, Alexandre Moulin, Caroline A Schmitt, Jean Pierre Caujolle, Célia Maschi, Marina Marinkovic, Azzam F Taktak, Heinrich Heimann, Bertil E Damato, Sarah E Coupland

Department of Clinical Medicine

20 Citations (Scopus)

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.

Original language	English
Journal	Pigment Cell & Melanoma Research
Volume	32
Issue number	4
Pages (from-to)	564-575
ISSN	1755-1471
DOIs	https://doi.org/10.1111/pcmr.12767
Publication status	Published - Jul 2019

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Kenawy, N., Kalirai, H., Sacco, J. J., Lake, S. L., Heegaard, S., Larsen, A.-C., Finger, P. T., Milman, T., Chin, K., Mosci, C., Lanza, F., Moulin, A., Schmitt, C. A., Caujolle, J. P., Maschi, C., Marinkovic, M., Taktak, A. F., Heimann, H., Damato, B. E., & Coupland, S. E. (2019). Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome. Pigment Cell & Melanoma Research, 32(4), 564-575. https://doi.org/10.1111/pcmr.12767

Kenawy, N, Kalirai, H, Sacco, JJ, Lake, SL, Heegaard, S, Larsen, A-C, Finger, PT, Milman, T, Chin, K, Mosci, C, Lanza, F, Moulin, A, Schmitt, CA, Caujolle, JP, Maschi, C, Marinkovic, M, Taktak, AF, Heimann, H, Damato, BE & Coupland, SE 2019, 'Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome', Pigment Cell & Melanoma Research, vol. 32, no. 4, pp. 564-575. https://doi.org/10.1111/pcmr.12767

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

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.",

author = "Nihal Kenawy and Helen Kalirai and Sacco, {Joseph J} and Lake, {Sarah L} and Steffen Heegaard and Ann-Cathrine Larsen and Finger, {Paul T} and Tatyana Milman and Kimberly Chin and Carlo Mosci and Francesco Lanza and Alexandre Moulin and Schmitt, {Caroline A} and Caujolle, {Jean Pierre} and C{\'e}lia Maschi and Marina Marinkovic and Taktak, {Azzam F} and Heinrich Heimann and Damato, {Bertil E} and Coupland, {Sarah E}",

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year = "2019",

month = jul,

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language = "English",

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pages = "564--575",

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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

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.

U2 - 10.1111/pcmr.12767

DO - 10.1111/pcmr.12767

M3 - Journal article

C2 - 30672666

SN - 1755-1471

VL - 32

SP - 564

EP - 575

JO - Pigment Cell & Melanoma Research

JF - Pigment Cell & Melanoma Research

IS - 4

ER -

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

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