Pilocytic astrocytoma (PA) is a primarily pediatric brain tumor caused mainly by mutations in the BRAF gene. In fact, there are two specific mechanisms for activation of BRAF implicated in PA formation: by fusion of the gene with nearby gene KIAA1549 (K:B fusion) or by point mutations of the BRAF gene itself. Research presented at the American Society for Clinical Oncology (ASCO) Annual Meeting 2014 used a newly designed test for K:B fusion to show that point mutations lead to a more dangerous form of the disease than does K:B fusion.
"Overall, the prognosis for Pilocytic astrocytoma is fairly good. But then we see about 10 percent of cases in which the disease acts more aggressively. What we show is that the non-aggressive and aggressive forms of the disease are, in fact, created by related but distinctly different genetic abnormalities," says Marileila Garcia, PhD, investigator at the University of Colorado Cancer Center and professor at the CU School of Medicine.
The test developed by Garcia for the current study used fluorescent in situ hybridization (FISH) to visualize BRAF and its fusion partner KIAA1549 inside cells, allowing researchers to see when these genes were fused together and when they were apart. In 64 patient samples, Garcia and colleagues found 37 that were K:B fusion positive and 27 that were negative. These two patient populations were markedly different. The mean age of the K:B fusion population was 7.4 years old, compared to 15.2 years old in the non-K:B population; 73 percent of the K:B PAs were found in the cerebellum, whereas 78 percent of the non-K:B PAs were found elsewhere; and non-K:B PAs were much more likely associated with co-occurrence of the disease Type 1 Neurofibromatosis, which can lead to the formation of additional tumors.
The distinction between these two pathways may help to explain the difference between outcomes for younger and older patients – PA in younger patients is more likely to be caused by K:B fusion and 5-year survival is generally high; PA in older patients is more likely to be caused by BRAF point mutations and 5-year survival is generally lower.
"Now that we have a reliable method for detecting K:B fusions in these patients, we may be able to more reliably decide how to treat PA. Patients without K:B fusions have a poor prognosis and should be treated most aggressively," Garcia says.
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Pilocytic astrocytoma (PA) is a primarily pediatric brain tumor caused mainly by mutations in the BRAF gene. In fact, there are two specific mechanisms for activation of BRAF implicated in PA formation: by fusion of the gene with nearby gene KIAA1549 (K:B fusion) or by point mutations of the BRAF gene itself. Research presented at the American Society for Clinical Oncology (ASCO) Annual Meeting 2014 used a newly designed test for K:B fusion to show that point mutations lead to a more dangerous form of the disease than does K:B fusion.
"Overall, the prognosis for Pilocytic astrocytoma is fairly good. But then we see about 10 percent of cases in which the disease acts more aggressively. What we show is that the non-aggressive and aggressive forms of the disease are, in fact, created by related but distinctly different genetic abnormalities," says Marileila Garcia, PhD, investigator at the University of Colorado Cancer Center and professor at the CU School of Medicine.
The test developed by Garcia for the current study used fluorescent in situ hybridization (FISH) to visualize BRAF and its fusion partner KIAA1549 inside cells, allowing researchers to see when these genes were fused together and when they were apart. In 64 patient samples, Garcia and colleagues found 37 that were K:B fusion positive and 27 that were negative. These two patient populations were markedly different. The mean age of the K:B fusion population was 7.4 years old, compared to 15.2 years old in the non-K:B population; 73 percent of the K:B PAs were found in the cerebellum, whereas 78 percent of the non-K:B PAs were found elsewhere; and non-K:B PAs were much more likely associated with co-occurrence of the disease Type 1 Neurofibromatosis, which can lead to the formation of additional tumors.
The distinction between these two pathways may help to explain the difference between outcomes for younger and older patients – PA in younger patients is more likely to be caused by K:B fusion and 5-year survival is generally high; PA in older patients is more likely to be caused by BRAF point mutations and 5-year survival is generally lower.
"Now that we have a reliable method for detecting K:B fusions in these patients, we may be able to more reliably decide how to treat PA. Patients without K:B fusions have a poor prognosis and should be treated most aggressively," Garcia says.
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Two novel BRAF fusions were identified in melanomas previously considered to be negative for molecular targets, and melanomas with these fusions were found to be potentially sensitive to anticancer drugs called MEK inhibitors, ...
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May 31, 2014
A University of Colorado Cancer Center study presented at the 50th Annual Meeting of the American Society for Clinical Oncology (ASCO) draws a line from mutation of the gene NTRK1, to its role as an oncogene in non-small ...
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Mar 19, 2014
In a scientific first, the fusion of two genes, ALK and EML4, has been identified as the genetic driver in an aggressive type of thyroid cancer, according to a study by the Translational Genomics Research Institute (TGen).
Study offers clues to cause of kids' brain tumors
Nov 16, 2012
(Medical Xpress)—Insights from a genetic condition that causes brain cancer are helping scientists better understand the most common type of brain tumor in children.
Gene-based test identifies poor-prognosis colon cancers
Mar 09, 2012
(HealthDay) -- A sensitive and specific gene-based classifier can be used to identify BRAF mutant colon cancer tumors and a subpopulation of BRAF wild-type tumors with poor prognosis, according to a study pu ...
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