title: HABP2 G534E Variant in Papillary Thyroid Carcinoma.
abstract: The main nonmedullary form of thyroid cancer is papillary thyroid carcinoma (PTC) that accounts for 80-90% of all thyroid malignancies. Only 3-10% of PTC patients have a positive family history of PTC yet the familiality is one of the highest of all cancers as measured by case control studies. A handful of genes have been implicated accounting for a small fraction of this genetic predisposition. It was therefore of considerable interest that a mutation in the HABP2 gene was recently implicated in familial PTC. The present work was undertaken to examine the extent of HABP2 variant involvement in PTC. The HABP2 G534E variant (rs7080536) was genotyped in blood DNA from 179 PTC families (one affected individual per family), 1160 sporadic PTC cases and 1395 controls. RNA expression of HABP2 was tested by qPCR in RNA extracted from tumor and normal thyroid tissue from individuals that are homozygous wild-type or heterozygous for the variant. The variant was found to be present in 6.1% familial cases, 8.0% sporadic cases (2 individuals were homozygous for the variant) and 8.7% controls. The variant did not segregate with PTC in one large and 6 smaller families in which it occurred. In keeping with data from the literature and databases the expression of HABP2 was highest in the liver, much lower in 3 other tested tissues (breast, kidney, brain) but not found in thyroid. Given these results showing lack of any involvement we suggest that the putative role of variant HABP2 in PTC should be carefully scrutinized.
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Jerneja
authors.initials: J
authors.lastname: Tomsic
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Fultz
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Sandya
authors.initials: S
authors.lastname: Liyanarachchi
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Huiling
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Internal Medicine, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Leigha
authors.initials: L
authors.lastname: Senter
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Albert
authors.initials: A
authors.lastname: de la Chapelle
mesh_terms: D002277:Carcinoma / Q000201:enzymology / Q000235:genetics*; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D020125:Mutation, Missense; D009928:Organ Specificity; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics*
chemical_list: C433550:HABP2 protein, human; D012697:Serine Endopeptidases