Genetic findings in treatment-naive and proton-beam-radiated iris melanomas

Krishna, Yamini, Kalirai, Helen ORCID: 0000-0002-4440-2576, Thornton, Sophie ORCID: 0000-0001-7693-7279, Damato, Bertil E, Heimann, Heinrich and Coupland, Sarah E ORCID: 0000-0002-1464-2069 (2016) Genetic findings in treatment-naive and proton-beam-radiated iris melanomas. BRITISH JOURNAL OF OPHTHALMOLOGY, 100 (7). pp. 1012-1016.

Text Genetic Findings in Iris Melanomas_BJO_revision 260216_MARKED COPY.docx - Author Accepted Manuscript Download (69kB)

Abstract

<h4>Background/aims</h4>Iris melanomas (IM) are rare and have a lower mortality than posterior uveal melanomas (UM). Our aims were to determine the prevalence of genetic changes associated with prognosis of posterior UM, in both treated and non-treated IM.<h4>Methods</h4>Retrospective database review and molecular analysis of all patients diagnosed with IM at the Liverpool Ocular Oncology Centre (LOOC) between 1993 and 2015. Archival pathology specimens of confirmed IM cases were analysed for chromosomal alterations, using multiplex ligation-dependent probe amplification (MLPA) or microsatellite analysis (MSA) depending on DNA yield, and <i>BRAF</i> mutation status.<h4>Results</h4>5189 patients were diagnosed with intraocular melanoma at LOOC from 1993 to 2015. Of these, 303 (5.8%) patients were diagnosed with IM. Tissue samples were available for 26 IM cases. Twelve of these cases had biopsies taken post-proton beam radiotherapy (PBR). Histological subtyping showed 14 IM being spindle, 2 epithelioid and 10 were of mixed cell type. Twenty of the 26 IM cases (77%) analysed genetically were classified as either disomy 3 (n=16) or monosomy 3 (n=4). Chromosome 6p gain was detected in 4/18 (22%) IM, and polysomy 8q in 6%. <i>BRAF</i> mutations were not detected in any of the four IM cases examined. One patient with IM died from metastatic disease: this tumour was disomy 3 with 6p and 8q gains. All other patients were alive with no evidence of metastases at study closure.<h4>Conclusions</h4>Chromosomal aberrations seen in posterior UM can also be demonstrated using MLPA or MSA in both treatment naïve and PBR-treated IM. Most IM display a low-metastatic risk chromosomal profile.

Item Type:	Article
Uncontrolled Keywords:	Iris, Humans, Melanoma, Uveal Neoplasms, Iris Neoplasms, Proto-Oncogene Proteins B-raf, DNA, Neoplasm, Biopsy, Prognosis, Retrospective Studies, DNA Mutational Analysis, Mutation, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Female, Male, Young Adult, Multiplex Polymerase Chain Reaction, Proton Therapy
Depositing User:	Symplectic Admin
Date Deposited:	18 Jul 2016 15:54
Last Modified:	19 Jan 2023 07:33
DOI:	10.1136/bjophthalmol-2015-308301
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3002407