title: Segregation and expression analyses of hyaluronan-binding protein 2 (HABP2): insights from a large series of familial non-medullary thyroid cancers and literature review.
abstract: BACKGROUND
  Recently, the G534E variant of the HABP2 gene was reported as the underlying genetic defect in a large kindred with nonsyndromic familial nonmedullary thyroid cancer (FNMTC). Nevertheless, this postulated role was not confirmed in additional cohorts. Contrasting data are also available on HABP2 expression in the thyroid.
  
  
  OBJECTIVE
  To investigate HABP2 as a potential susceptibility gene in a large series of 27 unrelated families with FNMTC and to test its expression in thyroid tumour and matched normal tissues.
  
  
  RESULTS
  Three of the 27 FNMTC families (11·1%) carried the HABP2G534Evariant. The genotyping of these families showed that HABP2G534Edoes not segregate with cancer. Indeed, affected individuals not carrying HABP2G534Ewere identified, and the variant was present also in members without thyroid cancer. HABP2 mRNA had a very variable expression in tissues from FNMTC, sporadic papillary thyroid cancers (PTCs) or contralateral normal tissues, by either nonquantitative or quantitative RT-polymerase chain reaction. In almost all cases, the gene appeared down- or up-regulated in tumours with respect to the corresponding normal tissue. At immunohistochemistry, HABP2 was expressed in both tumour and matched control tissues, without differences between sporadic and familial cases.
  
  
  CONCLUSIONS
  This study on a wide series of FNMTC indicates that the HABP2G534Evariant is frequent, but does not segregate with the disease. Nevertheless, the dysregulation of HABP2 expression found in either sporadic or familial PTCs or normal thyroid tissues is consistent with similar findings in other malignancies and could indicate a role of this gene also in thyroid cancer.
authors.affiliation: Division of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy.|Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Colombo
authors.affiliation: Endocrine Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Muzza
authors.affiliation: Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Proverbio
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ercoli
authors.affiliation: Division of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Perrino
authors.affiliation: Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cirello
authors.affiliation: Endocrine Surgery Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Vicentini
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy.|Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrero
authors.affiliation: Division of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy.|Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: Laura
authors.identifier: http://orcid.org/0000-0001-5372-0982
authors.initials: L
authors.lastname: Fugazzola
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005190:Family; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010375:Pedigree; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000032:analysis / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; C433550:HABP2 protein, human; D012697:Serine Endopeptidases