title: HABP2 p.G534E variant in patients with family history of thyroid and breast cancer.
abstract: Familial Papillary Thyroid Carcinoma (PTC) has been described as a hereditary predisposition cancer syndrome associated with mutations in candidate genes including HABP2. Two of 20 probands from families with history of PTC and breast carcinoma (BC) were evaluated by whole exome sequencing (WES) revealing HABP2 p.G534E. Sanger sequencing was used to confirm the involvement of this variant in three families (F1: 7 relatives; F2: 3 and F3: 3). The proband and his sister (with no malignant tumor so far) from F1 were homozygous for the variant whereas one relative with PTC from F2 was negative for the variant. Although the proband of the F3 with PTC was HABP2 wild type, three relatives presented the variant. Five of 170 healthy Brazilian individuals with no family history of BC or PTC and three of 50 sporadic PTC presented the p.G534E. These findings suggested no association of this variant with our familial PTC cases. Genes potentially associated with deregulation of the extracellular matrix organization pathway (CTSB, TNXB, COL4A3, COL16A1, COL24A1, COL5A2, NID1, LOXL2, MMP11, TRIM24 and MUSK) and DNA repair function (NBN and MSH2) were detected by WES, suggesting that other cancer-associated genes have pathogenic effects in the risk of familial PTC development.
authors.affiliation: CIPE - International Research Center, A. C. Camargo Cancer Center, Sao Paulo, SP, Brazil.|Department of Urology, Faculty of Medicine, São Paulo State University, UNESP, Botucatu, SP, Brazil.
authors.forename: Maisa
authors.initials: M
authors.lastname: Pinheiro
authors.affiliation: Department of Urology, Faculty of Medicine, São Paulo State University, UNESP, Botucatu, SP, Brazil.
authors.forename: Sandra Aparecida
authors.initials: SA
authors.lastname: Drigo
authors.affiliation: CIPE - International Research Center, A. C. Camargo Cancer Center, Sao Paulo, SP, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Tonhosolo
authors.affiliation: Department of Genetics and Evolutionary Biology, University of Sao Paulo, USP, Sao Paulo, SP, Brazil.
authors.forename: Sonia C S
authors.initials: SCS
authors.lastname: Andrade
authors.affiliation: CIPE - International Research Center, A. C. Camargo Cancer Center, Sao Paulo, SP, Brazil.
authors.forename: Fabio Albuquerque
authors.initials: FA
authors.lastname: Marchi
authors.affiliation: Princess Margaret Cancer Centre, University Health Network and The University of Toronto, Toronto, ON, Canada.|Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.affiliation: Department of Head and Neck Surgery and Otorhinolaryngology, A. C. Camargo Cancer Center, Sao Paulo, SP, Brazil.
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowalski
authors.affiliation: CIPE - International Research Center, A. C. Camargo Cancer Center, Sao Paulo, SP, Brazil.|Division of Cancer Epidemiology and Genetics, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Achatz
authors.affiliation: CIPE - International Research Center, A. C. Camargo Cancer Center, Sao Paulo, SP, Brazil.|Department of Urology, Faculty of Medicine, São Paulo State University, UNESP, Botucatu, SP, Brazil.|Department of Clinical Genetics, Vejle Hospital, Institute of Regional Health Research, University of Southern Denmark, Vejle, Denmark.
authors.forename: Silvia Regina
authors.initials: SR
authors.lastname: Rogatto
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: C433550:HABP2 protein, human; D012697:Serine Endopeptidases
keywords: breast cancer; genetics; hereditary tumors; molecular markers; thyroid cancer