Carla Colombo1,2, Marina Muzza3, Maria Carla Proverbio2, Giulia Ercoli4, Michela Perrino1, Valentina Cirello2, Leonardo Vicentini5, Stefano Ferrero4,6, Laura Fugazzola1,2. 1. Division of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy. 2. Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 3. Endocrine Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy. 4. Division of Pathology, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy. 5. Endocrine Surgery Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy. 6. Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Abstract
INTRODUCTION: 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. OBJECTIVES: 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 HABP2G534E variant. The genotyping of these families showed that HABP2G534E does not segregate with cancer. Indeed, affected individuals not carrying HABP2G534E were 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 HABP2G534E variant 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.
INTRODUCTION: 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. OBJECTIVES: 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 HABP2G534E variant. The genotyping of these families showed that HABP2G534E does not segregate with cancer. Indeed, affected individuals not carrying HABP2G534E were 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 HABP2G534E variant 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: María Sánchez-Ares; Soledad Cameselle-García; Ihab Abdulkader-Nallib; Gemma Rodríguez-Carnero; Carolina Beiras-Sarasquete; José Antonio Puñal-Rodríguez; José Manuel Cameselle-Teijeiro Journal: Front Endocrinol (Lausanne) Date: 2022-02-28 Impact factor: 5.555