Gene in uveal melanoma linked to good prognosis
Recurrent mutations in SF3B1 in uveal melanoma
- Date : 21 Jan 2013
- Topic : Melanoma
Uveal melanoma is often fatal, but tumours with mutations in theSF3B1gene are more likely to have a good outcome, new research suggests. Scientists at Washington University School of Medicine reported their findings in the advance online edition of Nature Genetics.
The researchers found mutations in a geneSF3B1.According to senior author of the article, Anne Bowcock, PhD, professor of genetics, these mutations develop in this distinct subtype of melanoma. Uveal melanomas make up about 5% of all melanomas. In many patients, there are no symptoms, and the tumours become fatal when they spread to the liver. Several years ago, Dr Bowcock and the study’s lead author, Dr William Harbour, a former Washington University ophthalmology surgeon who is now at the University of Miami, identified a commonly mutated gene,BAP1,in patients with uveal melanoma. They foundBAP1alterations in about 80% of uveal melanomas with a poor prognosis (class II tumours). About 75% of patients with these tumours die within five years, a sharp contrast to the generally favourable outcomes of patients whose tumours don’t haveBAP1mutations (class I).
DNA sequencing in uveal melanoma
For the new study, Dr Bowcock and her colleagues initially sequenced the DNA of uveal melanomas from 18 patients whoseBAP1status was already known. Seven had noBAP1mutations (class I tumours), and 11 hadBAP1mutations (class II tumours). The researchers’ analysis uncovered alterations in theSF3B1gene in three of the patients. This is the first time mutations in this gene have been found in uveal melanoma.
As part of the current study, the researchers also looked forSF3B1mutations in uveal melanomas from 102 patients, finding it in nearly 20% of them. Mutations in the gene were linked to favourable features, including a younger age at diagnosis and a far lower metastasis rate. Interestingly,SF3B1mutations always occurred at the same site of the gene. And theSF3B1andBAP1mutations were found to be almost mutually exclusive, meaning that if patients had a mutation in one of the genes, they were unlikely to have a mutation in the other. This suggests mutations in these genes may represent alternative pathways in tumour progression.
TheSF3B1gene also has been reported recently by other researchers to be mutated in myelodysplastic syndrome. For these patients,SF3B1mutations mean the condition is less likely to develop into a full-blown leukaemia. Changes in theSF3B1gene also have been found in chronic lymphocytic leukaemia and less frequently in breast cancer and other solid tumours. The gene’s link to prognosis is unclear for these cancers.
Normally, theSF3B1gene is involved in converting RNA into messenger RNA. This messenger molecule carries DNA’s code and serves as a template for making proteins. The researchers don’t yet understand how mutations in this gene are involved in cancer but it’s the next step of their research. They want to understand the functional consequences of mutations inSF3B1.
How are changes in this gene linked to cancer development?
This is the fourth gene known to be mutated in uveal melanoma along withBAP1and the genesGNAQandGNA11. A complete understanding of the molecular basis of this tumour type will be invaluable in predicting prognosis and in the identification and development of novel treatments.
The research is supported by grants from the USA National Institutes of Health (NIH) (R01 CA16187001 and CA12597007), the Melanoma Research Alliance, the Melanoma Research Foundation, the Tumori Foundation, Research to Prevent Blindness, Inc., and awards to the Department of Ophthalmology and Visual Sciences at Washington University from a Research to Prevent Blindness, Inc., unrestricted grant and also the NIH Vision Core grant (P30 EY02687c) and an NIH training grant (5 T32 AR007279-32).
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