NCI Scientists Map Genetic Changes in Rhabdomyosarcoma Tumors
Researchers from the National Cancer Institute (NCI) have found two distinct genotypes in rhabdomyosarcoma tumors: those characterized by the PAX3 or PAX7 fusion and those that lack these fusions but harbor mutations in key signaling pathways. The discovery could lead to the development of targeted diagnostic tools and treatments for children with the cancer. The study is published in Cancer Discovery.
According to the NCI, rhabdomyosarcoma is the most common type of soft-tissue sarcoma in children, and can occur anywhere in the body. The cancer has a dismal survival outcome in those patients with metastatic disease, with just 30% surviving 5 years with aggressive treatment. To determine the genetic events that contribute to rhabdomyosarcoma, scientists from the NCI, in collaboration with the Children’s Oncology Group and the Broad Institute, performed whole-genome, whole-exome, and transcriptome sequencing on 147 rhabdomyosarcoma tumors, which were paired with normal tissue samples.
Study Findings
In addition to the genotypes characterized by the PAX3 or PAX7 fusion and those that lack these fusions but harbor mutations in key signaling pathways, the scientists found that the overall burden of somatic mutations in the cancer is relatively low, especially in tumors that harbor a PAX3/7 gene fusion. They also found novel recurrent mutations in FBXW7 and BCOR, in addition to previously reported mutations in several genes in rhabdomyosarcoma, including NRAS, KRAS, HRAS, FGFR4, PIK3CA, and CTNNB1; these findings may provide the possibility for new therapies.
Moreover, the researchers identified mutations in additional genes in the RAS/PIK3CA signaling pathway. Overall, alterations in this pathway were found in 93% of rhabdomyosarcoma tumors.
“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 treatment options currently available for pediatric patients with rhabdomyosarcoma,” Jack F. Shern, MD, a Clinical Fellow at the NCI and lead author of the study, said in a statement.
Javed Khan, MD, of the Center for Cancer Research, National Institutes of Health, is corresponding author of the Cancer Discovery article. Dr. Khan and Li Chen, PhD, also of the Center for Cancer Research, contributed equally to the article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
