From Healio - HemOncToday

Genetic mutations identified in rhabdomyosarcoma tumors
Shern JF. Cancer Discov.2014;4:216-231.

February 14, 2014
Newly discovered recurrent mutations in the genes FBXW7 and BCOR in rhabdomyosarcoma may offer new therapeutic options and improve outcomes for this type of pediatric cancer, according to results of a study conducted by NCI.

Researchers also found that the receptor tyrosine kinase RAS/PIK3CA axis is altered in 93% of rhabdomyosarcoma cases, a finding they say supports the use of future genomics-based therapies.

In a collaborative effort between the NCI, the Children’s Oncology Group, and the Broad Institute of the Massachusetts Institute of Technology and Harvard University, the researchers conducted whole-genome sequencing on 14 rhabdomyosarcoma tumors matched with normal tissue samples. Whole-exome and transcriptome sequencing also was performed.

The researchers classified two genotypes of rhabdomyosarcoma tumors: PAX gene fusion-positive tumors and PAX gene fusion-negative tumors. They determined that the PAX gene fusion-negative tumors exhibited significantly higher rates of somatic mutation than the PAX gene fusion-positive tumors, and that the RAS pathway is mutationally activated in at least 45% of PAX gene fusion-negative tumors.

Researchers also confirmed previous findings of frequent somatic mutations in the genes NRAS, KRAS, HRAS, FGFR4, PIK3CA and CTNNB, and reported novel mutations in FBXW7 and BCOR.

“Although more work is needed, our study may provide researchers with the rationale to develop genomics-guided therapeutic interventions with greater efficacy and fewer side effects than the treatments options currently available for pediatric patients with rhabdomyosarcoma,” Jack Shern, MD, a clinical fellow at the NCI, said in a press release.

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Disclosure: Researchers reported employment relationships, ownerships interests and consultant/advisory board positions with Foundation Medicine.