The study, published in the journal Nature Communications, may pave the way for the development of medicines to suppress a fatal type of tumor before it spreads to other parts of the body.
A molecular mechanism that drives the progression of uveal melanoma (UM), an often fatal eye disease in adults, has been found by researchers.
It also offers a breakthrough in cancer biology, connecting two cancer hallmarks — chromosomal instability (errors in chromosome segregation during cell division) and epigenetic modifications (changes in gene regulation) — that combine to accelerate disease development.
UMs develop within the eye tissue, most commonly in aged persons and people with fair complexion. Every year, approximately 2,500 cases of UM are reported in the United States.
Surgery and radiation are the most often used treatments for UM. However, once the UM has progressed to other organs, the prospects of survival are low.
“Up to half of UM patients are prone to developing liver metastasis, which is usually lethal,” said Mathieu Bakhoum co-first author of the study.
“The reasons why only a group of patients with certain tumor characteristics develop metastasis, and the mechanisms driving metastasis, are unknown, yet crucial to developing target therapies to this lethal disease.”
The researchers used a combination of genomic and other investigations at the single-cell level to show that the loss of Polycomb Repressive Complex 1 – proteins that regulate gene expression — accelerates UM progression.
This loss results in abnormal gene expression and abnormalities in chromosome segregation during cell division. This eventually causes an inflammatory reaction, which makes the tumour more aggressive.
“By uncovering key steps involved in tumor progression, our work highlights an opportunity for earlier therapeutic intervention to suppress tumor evolution,” Bakhoum said.
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