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Updated: Mar 30, 2026
Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma
Published on: January 25, 2015
Insights into genetic alterations of liver metastases from uveal melanoma
Conni McCarthy1, Helen Kalirai1, Sarah L Lake1
1Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Abstract:
The liver is the organ usually affected by metastatic uveal melanoma (MUM). Current treatments are almost always ineffective and mortality remains high. In this study, copy number variations (CNVs) were identified in 12 metastatic and five matched primary UMs (PUMs). Our data revealed a wide spectrum of genetic alterations in MUM. Most common were amplifications of chromosome (chr.) 8q; alterations on chr. 3 included monosomy, isodisomy, and large regions of homozygosity (ROH). Genomic profiles of PUM-MUM pairs varied in their degree of similarity and complexity. However, within the pairs, 135 genes were consistently altered. Protein expression of C-MYC and BAP1 was examined by immunohistochemistry (IHC); a positive association between IHC and CNVs was seen for C-MYC. This comprehensive catalogue of CNVs associated with MUM should facilitate the identification of key alterations that drive tumor growth. This would have the potential to select urgently needed novel, targeted, therapeutic regimens.
Insights
Copy number variations (CNVs) in metastatic uveal melanoma (MUM) were identified, revealing frequent alterations like chromosome 8q amplifications. This genetic catalog may guide new targeted therapies for this aggressive cancer.
Area of Science:
- Oncology
- Genetics
- Genomics
Background:
- Metastatic uveal melanoma (MUM) frequently affects the liver, with current treatments showing limited efficacy and high mortality rates.
- Understanding the genetic landscape of MUM is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To identify and characterize copy number variations (CNVs) in metastatic uveal melanoma (MUM) and matched primary uveal melanomas (PUMs).
- To correlate genetic alterations with protein expression and identify potential therapeutic targets.
Main Methods:
- Comparative genomic hybridization (CGH) or similar techniques to analyze CNVs in 12 MUM and 5 PUM samples.
- Immunohistochemistry (IHC) to assess protein expression of C-MYC and BAP1.
- Bioinformatic analysis to identify consistently altered genes and genomic profiles.
Main Results:
- A broad range of genetic alterations were observed in MUM, with common findings including chromosome 8q amplifications and alterations on chromosome 3 (monosomy, isodisomy, regions of homozygosity).
- Genomic profiles of primary and metastatic tumors showed variable similarity, but 135 genes were consistently altered across matched pairs.
- A positive association was found between C-MYC protein expression (via IHC) and CNVs, suggesting a link between genetic changes and protein levels.
Conclusions:
- This study provides a comprehensive catalog of CNVs in MUM, highlighting key genetic alterations driving tumor progression.
- The identified genetic alterations and their associated protein expression patterns offer potential targets for novel, targeted therapeutic regimens in MUM.
- Further research into these CNVs could significantly improve treatment strategies and patient outcomes for metastatic uveal melanoma.
