Functional impact of a germline RET mutation in alveolar rhabdomyosarcoma.

Specific mutations in the proto-oncogene are associated with multiple endocrine neoplasia type 2A, a hereditary syndrome characterized by tumorigenesis in multiple glandular elements. In rare instances, MEN2A-associated germline mutations have also occurred with non-MEN2A associated cancers. One such germline mutant mutation occurred concomitantly in a young adult diagnosed with alveolar rhabdomyosarcoma, a pediatric and young adult soft-tissue cancer with a generally poor prognosis. Although tumor tissue samples were initially unable to provide a viable cell culture for study, tumor tissues were sequenced for molecular characteristics. Through a hierarchical clustering approach, the index case sample was matched to several genetically similar cell models, which were transformed to express the same mutant RET as the index case and used to explore potential therapeutic options for mutant -bearing alveolar rhabdomyosarcoma. We also determined whether the mutation associated with the index case caused synthetic lethality to select clinical agents. From our investigation, we did not identify synthetic lethality associated with the expression of that patient's variant, and overall we did not find experimental evidence for the role of in rhabdomyosarcoma progression.