Cluster analysis of multiplex ligation-dependent probe amplification data in choroidal melanoma

Area of Science:

• Ophthalmology
• Genetics
• Oncology

Background:

• Choroidal melanoma (CM) is a rare intraocular malignancy.
• Multiplex ligation-dependent probe amplification (MLPA) is a technique used to detect copy number variations.
• Chromosomes 3 and 8q are known to be associated with CM patient survival.

Purpose of the Study:

• To investigate correlations within MLPA data for choroidal melanoma (CM).
• To assess the prognostic significance of these correlations for patient survival.
• To explore underlying genetic structures in CM using unsupervised clustering.

Main Methods:

• MLPA data from 602 CM patients across 31 loci on chromosomes 1p, 3, 6, and 8 were analyzed.
• Unsupervised k-means clustering and Principal Component Analysis (PCA) were employed to identify patterns.
• Survival analyses (Kaplan-Meier, log-rank) were performed on identified clusters.
• Correlation with largest basal tumor diameter (LTD) was examined.

Main Results:

• Chromosome 3 analysis revealed two distinct clusters (monosomy/disomy 3) with significantly different survival (5-year survival: 80% vs. 40%).
• PCA indicated that chromosome 3 bimodality was captured by the first principal component.
• Combining chromosome 3 clusters with 8q gain identified three prognostic groups with 5-year survival rates of ~97%, 80%, and 30%.

Conclusions:

• The observed bimodality in chromosome 3 MLPA data likely represents complete monosomy or disomy 3.
• Chromosome 3 cluster membership and 8q gain have comparable prognostic impact.
• Largest basal tumor diameter (LTD) may act as a confounding factor in survival predictions.