RET proto-oncogene in the development of human cancer.
The RET proto-oncogene, located on chromosome subband 10q11.2, encodes a receptor tyrosine kinase expressed in tissues and tumors derived from neural crest. Germline (present in every cell of the body) mutations in RET cause multiple endocrine neoplasia type 2 (MEN 2), an inherited cancer syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PC), and hyperparathyroidism (HPT). This knowledge has allowed molecular diagnosis and presymptomatic DNA-based testing to become possible. RET testing is considered the standard of care in MEN 2 families because clinical decisions are made based on the results of such gene testing. There appears to be a correlation between specific RET mutation type and organ-specific tumor development. Such knowledge might be useful in tailoring targeted surveillance in the near future. Somatic (in the tumor only) RET mutations have been found in a proportion of sporadic MTCs and PCs. Whether the presence of somatic RET mutation is associated with a poor prognosis is currently being investigated as another tool for molecular medicine.
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Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. eng-1@medctr.osu.edu
D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000235:genetics; D029721:Drosophila Proteins; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006627:Hirschsprung Disease / Q000235:genetics; D006801:Humans; D018813:Multiple Endocrine Neoplasia Type 2a / Q000175:diagnosis / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics*
D029721:Drosophila Proteins; D005819:Genetic Markers; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila