Common alleles of predisposition in endocrine neoplasia.
The identification of germline high penetrance gain-of-function mutations in the RET proto-oncogene as causative of multiple endocrine neoplasia led to accurate molecular diagnosis, predictive testing and gene-informed preventative medicine. Many syndromic endocrine neoplasias fell under this clinically utile model, although not all endocrine neoplasias were accounted for by these high penetrance predisposition genes associated with the validated practice of clinical cancer genetics. The past decade has seen the identification of low penetrance alleles for various endocrine neoplasias, including medullary and epithelial thyroid carcinomas and isolated pituitary adenomas. Functional characterisation of these effects, which range from subtle expressional or micro-RNA regulation, and the analysis of the conferred risks, which are typically low and below the threshold for medical actionability, remain scientific challenges before these may be incorporated into routine clinical practice.
Eng
Charis
C
Genomic Medicine Institute, Lerner Research Institute and Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA. engc@ccf.org
D000483:Alleles; D018276:Carcinoma, Medullary / Q000235:genetics; D004701:Endocrine Gland Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009377:Multiple Endocrine Neoplasia / Q000235:genetics; D019683:Penetrance; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human