Familial non-medullary thyroid cancer: unraveling the genetic maze
- 1 December 2016
- journal article
- review article
- Published by Bioscientifica in Endocrine-Related Cancer
- Vol. 23 (12), R577-R595
- https://doi.org/10.1530/erc-16-0067
Abstract
Familial non-medullary thyroid cancer (FNMTC) constitutes 3–9% of all thyroid cancers. Out of all FNMTC cases, only 5% in the syndromic form has well-studied driver germline mutations. These associated syndromes include Cowden syndrome, familial adenomatous polyposis, Gardner syndrome, Carney complex type 1, Werner syndrome and DICER1 syndrome. It is important for the clinician to recognize these phenotypes so that genetic counseling and testing can be initiated to enable surveillance for associated malignancies and genetic testing of family members. The susceptibility chromosomal loci and genes of 95% of FNMTC cases remain to be characterized. To date, 4 susceptibility genes have been identified (SRGAP1 gene (12q14), TITF-1/NKX2.1 gene (14q13), FOXE1 gene (9q22.33) and HABP2 gene (10q25.3)), out of which only the FOXE1 and the HABP2 genes have been validated by separate study groups. The causal genes located at the other 7 FNMTC-associated chromosomal loci (TCO (19q13.2), fPTC/ PRN (1q21), FTEN (8p23.1-p22), NMTC1 (2q21), MNG1 (14q32), 6q22, 8q24) have yet to be identified. Increasingly, gene regulatory mechanisms (miRNA and enhancer elements) are recognized to affect gene expression and FNMTC tumorigenesis. With newer sequencing technique, along with functional studies, there has been progress in the understanding of the genetic basis of FNMTC. In our review, we summarize the FNMTC studies to date and provide an update on the recently reported susceptibility genes including novel germline SEC23B variant in Cowden syndrome, SRGAP1 gene, FOXE1 gene and HABP2 genes in non-syndromic FNMTC.Keywords
This publication has 100 references indexed in Scilit:
- Germline SDHx variants modify breast and thyroid cancer risks in Cowden and Cowden-like syndrome via FAD/NAD-dependant destabilization of p53Human Molecular Genetics, 2011
- Prevalence, Clinicopathologic Features, and Somatic Genetic Mutation Profile in Familial Versus Sporadic Nonmedullary Thyroid CancerThyroid®, 2011
- A Clinical Scoring System for Selection of Patients for PTEN Mutation Testing Is Proposed on the Basis of a Prospective Study of 3042 ProbandsAmerican Journal of Human Genetics, 2011
- DICER1 Mutations in Familial Multinodular Goiter With and Without Ovarian Sertoli-Leydig Cell TumorsJAMA, 2011
- Carney complex and other conditions associated with micronodular adrenal hyperplasiasBest Practice & Research Clinical Endocrinology & Metabolism, 2010
- Germline Epigenetic Regulation of KILLIN in Cowden and Cowden-like SyndromeJAMA, 2010
- Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populationsNature Genetics, 2009
- A Susceptibility Locus for Papillary Thyroid Carcinoma on Chromosome 8q24Cancer Research, 2009
- Germline Mutations and Variants in the Succinate Dehydrogenase Genes in Cowden and Cowden-like SyndromesAmerican Journal of Human Genetics, 2008
- Killin is a p53-regulated nuclear inhibitor of DNA synthesisProceedings of the National Academy of Sciences of the United States of America, 2008