Mendelian genetics of rare-and not so rare-cancers
- 28 September 2010
- journal article
- review article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 1214 (1), 70-82
- https://doi.org/10.1111/j.1749-6632.2010.05789.x
Abstract
Mendelian genetics forms the basis for gene-informed risk assessment and management for the patient and family, and should be at the very foundation of 21st century personalization of healthcare. Yet this is an underutilized commodity. Identification and characterization of germline mutations in the RET proto-oncogene, encoding a receptor tyrosine kinase, as causing >90% of multiple endocrine neoplasia type 2 (MEN 2), an autosomal dominant disorder characterized by medullary thyroid cancer, pheochromocytoma, and hyperparathyroidism, heralded the era of evidence-based molecular diagnosis, predictive testing, genetic counseling, gene-informed cancer risk assessment, and preventative medicine. Since then, many syndromic endocrine neoplasias have proven to fall under this clinically utile and actionable model, such as those caused by mutations in RET, VHL, or SDHB-D. The familial risk associated with epithelial (nonmedullary) thyroid carcinoma is among the highest of all solid tumors, yet only a few highly penetrant heritable epithelial thyroid cancer syndrome exist. This is illustrated by Cowden syndrome, a difficult-to-recognize autosomal dominant disorder characterized by breast, thyroid, and other cancers, caused by germline mutations in PTEN, encoding a phosphatase, and minorly, SDHB/SDHD variants.Keywords
This publication has 75 references indexed in Scilit:
- Frequent Gastrointestinal Polyps and Colorectal Adenocarcinomas in a Prospective Series of PTEN Mutation CarriersGastroenterology, 2010
- Germline mutations in TMEM127 confer susceptibility to pheochromocytomaNature Genetics, 2010
- Pathogenicity of DNA Variants and Double Mutations in Multiple Endocrine Neoplasia Type 2 and Von Hippel-Lindau SyndromeJournal of Clinical Endocrinology & Metabolism, 2010
- SDH5 , a Gene Required for Flavination of Succinate Dehydrogenase, Is Mutated in ParagangliomaScience, 2009
- Estimation of absolute risk for prostate cancer using genetic markers and family historyThe Prostate, 2009
- The Approach to the Patient with ParagangliomaJournal of Clinical Endocrinology & Metabolism, 2009
- The Scientific Foundation for Personal Genomics: Recommendations from a National Institutes of Health–Centers for Disease Control and Prevention Multidisciplinary WorkshopGenetics in Medicine, 2009
- Guidelines for Genetic Risk Assessment of Hereditary Breast and Ovarian Cancer: Early Disagreements and Low UtilizationJournal of General Internal Medicine, 2009
- Germline Mutations and Variants in the Succinate Dehydrogenase Genes in Cowden and Cowden-like SyndromesAmerican Journal of Human Genetics, 2008
- Male breast cancer in Cowden syndrome patients with germline PTEN mutationsJournal of Medical Genetics, 2001