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Nihal Kenawy, Bertil E Damato, Sarah E Coupland, Sarah L Lake, Liverpool Ocular Oncology Research Group; Copy number variations in conjunctival melanoma detected by Single Nucleotide Polymorphism array. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1283.
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© ARVO (1962-2015); The Authors (2016-present)
Despite the evolving research into the molecular changes in conjunctival melanoma (CoM), the molecular etiology of this disease is still uncertain. In this study, we aimed to determine gene copy number variations (CNVs) occurring in CoM with a view to ultimately, identifying disease-specific biomarkers that could be used to develop prognostic testing, as has been achieved in uveal melanoma, and improve patient care.
In this study, 56 patients with primary CoM were recruited from five centres in Europe and the USA between 2005 and 2012. DNA was extracted from formalin-fixed, paraffin-embedded excised tumors. Sufficient DNA for analysis using the Affymetrix 6.0 Single Nucleotide Polymorphism (SNP) microarray was obtained from 33 samples. Data analysis was performed using the Partek Genomic suite of software.
Amplification of PIK3CA (3q26.32) and LRRC16A (6p22.2) was observed in 52% of patient samples. Less commonly, amplification of CDK6 (7q21.2), WISP1 (8q24.22) and KRAS (12p12.1) were detected in 48%, 45% and 36% of tumors, respectively. Recurrent deletions were detected in GPRIN2 (10q11.22) and JAK2 (9p24.1) in 39% of CoM. In addition, RET (10q11.21), WWOX (16q23.1), CELF4 (18q12.2) and BTNL8 (5q35.3), were deleted in 36% of the patient cohort. There was no statistical correlation between the frequency of genetic alterations in the CoM and whether they metastasized, were of epithelioid cell type, or arose in the caruncle. Amplification of TAF6L (11q12.3) was statistically significantly associated with non-bulbar tumor location (p=0.048, Fisher’s exact test).
This study improves our understanding of CoM pathogenesis by identifying CNVs, in individual genes, not previously detected in CoM. The observed alterations differ from those seen in both uveal and cutaneous melanomas, further suggesting different etiological mechanisms for each of these tumor types. Validation of the identified CNVs by an alternative methodology is needed, in addition to investigation of their biological significance to further improve our understanding of the molecular regulation of CoM development. This will facilitate the identification of patients at high-risk of recurrence or metastasis and, potentially, allow for the development of targeted therapies in CoM.
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