Cold Spring Harb Mol Case Stud
JMG, Animals, Cell Line, Tumor, DNA Mutational Analysis, Genotype, Germ Cells, Germ-Line Mutation, Humans, Mice, Multiple Endocrine Neoplasia Type 2a, Phenotype, Proto-Oncogene Proteins c-ret, Rhabdomyosarcoma, Alveolar, Xenograft Model Antitumor Assays
Cold Spring Harb Mol Case Stud 2021 Jun 11; 7(3):e006049
Specific mutations in the RET 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 RET mutations have also occurred with non-MEN2A associated cancers. One such germline mutant RET 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 RET-bearing alveolar rhabdomyosarcoma. We also determined whether the RET 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 RET variant, and overall we did not find experimental evidence for the role of RET in rhabdomyosarcoma progression.
Berlow, Noah E; Crawford, Kenneth A; Bult, Carol J; Noakes, Christopher; Sloma, Ido; Rudzinski, Erin R; and Keller, Charles, "Functional impact of a germline RET mutation in alveolar rhabdomyosarcoma." (2021). Faculty Research 2021. 306.