Abstract B15: Genomic classification and prognosis in rhabdomyosarcoma: A report from the Children’s Oncology Group, the Institute of Cancer Research, and the National Cancer Institute
| Autor: | Jack F. Shern, Janet Shipley, Susanne A. Gatz, Xinyu Wen, Anna Kelsey, Donald A. Barkauskas, David G. Hall, Joanna Selfe, Rebecca Brown, Julia C. Chisholm, Javed Khan, Douglas S. Hawkins, Meriel Jenney, Rajesh Patidar, Marielle E. Yohe, Corinne M. Linardic, Young Min Song, Jun Wei, Erin Rudinski, Stephen X. Skapek |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Cancer Research. 80:B15-B15 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.pedca19-b15 |
| Popis: | Purpose: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor and beyond PAX-FOXO1 fusion status, no genomic markers are available for risk stratification. We therefore performed a large-scale study through an international consortium to more accurately determine the incidence of driver mutations and their association with clinical outcome. Patients and Method: Formalin-fixed, paraffin-embedded material was collected from patients enrolled on Children’s Oncology Group trials and UK patients enrolled on MMT trials. Pathology was reviewed centrally and extracted DNA was subjected to targeted capture sequencing using a panel of 39 genes previously associated with RMS. Mutations, indels, deletions, gene amplifications, and copy number variation was called using analysis pipelines developed at the NCI. Results: DNA from six hundred and forty-one patients was suitable for analyses. A median of 1 variant call was found per tumor. Mutation of a RAS isoform was found in 29% of all fusion negative cases, mutation of a RAS pathway member was seen in greater than 50% of cases, and 24% had no putative driver mutation identified. BCOR (15%), NF1 (11%), and TP53 (12%) mutations were found at a higher incidence than previously reported. Interestingly, mutations in HRAS were notable in the infant population whereas those in NRAS were enriched in adolescents. Among infants < 1 year, 71% of cases harbored a mutation in HRAS or KRAS. In contrast, mutation of MYOD1 was associated with an older age and a head and neck primary site. Finally, 29% of the evaluated tumors harbored multiple driver mutations consistent with subclonal variation and tumor heterogeneity in fusion-negative RMS. Conclusion: This is the largest genomic characterization of clinically annotated RMS tumors to date and provides genetic features that refine risk stratification and can be incorporated into prospective trials. Citation Format: Jack Shern, Joanna Selfe, Rajesh Patidar, Young Song, Marielle Yohe, Jun Wei, Xinyu Wen, Erin Rudinski, Donald Barkauskas, David Hall, Corinne Linardic, Meriel Jenney, Julia Chisholm, Rebecca Brown, Anna Kelsey, Susanne Gatz, Stephen Skapek, Douglas Hawkins, Janet Shipley, Javed Khan. Genomic classification and prognosis in rhabdomyosarcoma: A report from the Children’s Oncology Group, the Institute of Cancer Research, and the National Cancer Institute [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B15. |
| Databáze: | OpenAIRE |
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