Avaliação de mutações nos genes supressores de tumor MEN1 e AIP em prolactinomas associados a síndromes familiais

Abstract

Pituitary adenomas are benign neoplasms that arise from the expansion of single cells from the adeno-pituitary. These tumors comprise 10 to 15% of all intracranial tumors. The pathogenic mechanisms of these tumors can be either genetic or epigenetic changes, resulting in the deregulation of cell cycle, signaling defects or loss of tumor suppressor factors. The prolactinoma is the most frequent pituitary adenoma, and may cause infertility. However, familial cases are rare and poorly characterized. Therefore, the propose of this work is to perform molecular characterization of two families that carry prolactinoma: family 1, which harbors familial isolated prolactinoma, and family 2, a familial multiple endocrine neoplasia type 1 case. We surveyed mutations in two tumor suppressor genes, AIP and MEN1. For this study, genomic DNA was extracted from affected as well as healthy members of both families. Sequencing was performed for the 9 coding exons of MEN1, and the 6 exons of AIP. Significant variants were not detected in MEN1 for neither tested samples from both families. Unexpectedly, there were no mutations on AIP in family 1, but the multiple endocrine neoplasia type 1 patient has the genetic variation p.R16H in exon 1 of AIP. Considering the related results, no correlations were detected between mutations in the selected genes and prolactinoma development in family 1. The rule of p.R16H variant in pituitary adenoma development in family 2 patient needs further investigation.