Compound HRAS/PIK3CA mutations in Chinese patients with alveolar rhabdomyosarcomas
Chun-Xia Liu1, Xiao-Ying Li, Cheng-Fang Li
1Department of Pathology, Shihezi University School of Medicine, Shihezi, China
Abstract:
The rhabdomyosarcoma (RMS) is the most common type of soft tissue tumor in children and adolescents; yet only a few screens for oncogenic mutations have been conducted for RMS. To identify novel mutations and potential therapeutic targets, we conducted a high-throughput Sequenom mass spectrometry-based analysis of 238 known mutations in 19 oncogenes in 17 primary formalin-fixed paraffin-embedded RMS tissue samples and two RMS cell lines. Mutations were detected in 31.6% (6 of 19) of the RMS specimens. Specifically, mutations in the NRAS gene were found in 27.3% (3 of 11) of embryonal RMS cases, while mutations in NRAS, HRAS, and PIK3CA genes were identified in 37.5% (3 of 8) of alveolar RMS (ARMS) cases; moreover, PIK3CA mutations were found in 25% (2 of 8) of ARMS specimens. The results demonstrate that tumor profiling in archival tissue samples is a useful tool for identifying diagnostic markers and potential therapeutic targets and suggests that these HRAS/ PIK3CA mutations play a critical role in the genesis of RMS.
Insights
Rhabdomyosarcoma (RMS) research identified mutations in key genes like NRAS, HRAS, and PIK3CA in pediatric soft tissue tumors. This study highlights archival tissue analysis for discovering diagnostic markers and therapeutic targets in RMS.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Rhabdomyosarcoma (RMS) is a prevalent pediatric soft tissue sarcoma.
- Limited genomic profiling has been performed on RMS, hindering the identification of therapeutic targets.
Purpose of the Study:
- To identify novel oncogenic mutations in RMS.
- To explore potential therapeutic targets for RMS treatment.
- To assess the utility of archival tissue samples for molecular profiling.
Main Methods:
- High-throughput Sequenom mass spectrometry was employed.
- Analysis focused on 238 known mutations across 19 oncogenes.
- Samples included 17 primary formalin-fixed paraffin-embedded RMS tissues and 2 RMS cell lines.
Main Results:
- Mutations were detected in 31.6% of RMS specimens analyzed.
- NRAS mutations were found in embryonal RMS (27.3%).
- NRAS, HRAS, and PIK3CA mutations were identified in alveolar RMS (ARMS) (37.5%), with PIK3CA mutations present in 25% of ARMS cases.
Conclusions:
- Tumor profiling of archival tissues is effective for identifying diagnostic markers and therapeutic targets in RMS.
- HRAS and PIK3CA mutations appear critical in the development of RMS.
- This research provides insights into the genetic landscape of RMS, paving the way for targeted therapies.
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