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Updated: May 31, 2026
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Multiplex ligation-dependent probe amplification of conjunctival melanoma reveals common BRAF V600E gene mutation and
Sarah L Lake1, Fidan Jmor, Justyna Dopierala
1Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom. s.l.lake@liv.ac.uk
Purpose:
To determine the occurrence of BRAF V600E gene mutations and copy number changes of all autosome arms and genes known to be frequently altered in tumorigenesis in primary and metastatic conjunctival melanomas (CoMs).
Methods:
DNA (200 ng) was analyzed by three multiplex ligation-dependent probe amplification assays (P027 uveal melanoma, P036 human telomere, and P206 spitzoid melanoma).
Results:
Eight of 16 primary tumor samples and 4 of 6 metastatic samples showed BRAF V600E gene mutations. CDKN1A and RUNX2 (both 6p21.2) were amplified in 11 and 16 of 21 primary CoMs, respectively. In metastatic CoMs, MLH1 (3p22.1) and TIMP2 (17q25.3) were frequently amplified, and MGMT (20q26.3) and ECHS1 (10q26.3) were frequently deleted. The BDH (3q), FLJ20265 (4p), OPRL1 (20q), and PAO (10q) genes, representing the telomeres of their respective chromosome arms in the P036 assay, were frequently amplified in metastatic CoMs. No statistically significant associations were identified between BRAF mutation or CDKN1A or RUNX2 amplification and sex, age, histologic cell type, or patient survival.
Conclusions:
No copy number changes were associated exclusively with metastatic CoMs. However, further investigation of the role of CDKN1A and RUNX2 in CoMs development and that of MLH1, TIMP2, MGMT, and ECHS1 in metastatic CoMs is warranted. Validation of the observed gene and chromosome arm copy number changes in a larger cohort of primary and metastatic CoMs is necessary to identify the patients at highest risk for CoMs metastasis.
Insights
BRAF V600E mutations and gene copy number alterations were identified in conjunctival melanomas (CoMs). Further research is needed to understand their role in CoMs development and metastasis risk.
Area of Science:
- Oncology
- Genetics
- Ophthalmology
Background:
- Conjunctival melanoma (CoM) is a rare ocular malignancy.
- Understanding the genetic landscape of CoM is crucial for diagnosis and treatment.
Purpose of the Study:
- To investigate BRAF V600E mutations in CoM.
- To analyze copy number changes in autosome arms and key tumorigenesis genes in primary and metastatic CoMs.
Main Methods:
- DNA from 21 primary and 6 metastatic CoMs was analyzed.
- Three multiplex ligation-dependent probe amplification assays were employed.
Main Results:
- BRAF V600E mutations were found in 8/16 primary and 4/6 metastatic CoMs.
- CDKN1A and RUNX2 amplifications were common in primary CoMs.
- MLH1, TIMP2, MGMT, and ECHS1 alterations were frequent in metastatic CoMs.
Conclusions:
- No copy number changes were exclusively linked to metastatic CoMs.
- Further study of CDKN1A, RUNX2, MLH1, TIMP2, MGMT, and ECHS1 in CoM is warranted.
- Larger cohort validation is needed to identify metastasis risk markers.
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