Please use this identifier to cite or link to this item:
Title: Possible role of a radiation-induced p53 mutation in a Nelson's syndrome patient with a fatal outcome
Authors: PINTO, Emilia ModoloSIQUEIRA, Sheila A. C.CUKIER, PriscillaFRAGOSO, Maria C. B. V.LIN, Chin JiaMENDONCA, Berenice Bilharinho de
Citation: PITUITARY, v.14, n.4, p.400-404, 2011
Abstract: Nelson's syndrome (NS) is characterized by the appearance and/or progression of ACTH-secreting pituitary macroadenomas in patients who had previously undergone bilateral adrenalectomy for the treatment of Cushing's disease. Such corticotroph macroadenomas respond poorly to currently available therapeutic options which include surgery, radiotherapy and chemotherapy. P53 protein accumulation may be detected by immunohistochemistry in pituitary corticotroph adenomas and it has been suggested that it might be causally related to tumor development. Wild type P53 protein plays an important role in the cellular response to ionizing radiation and other DNA damaging agents and is mutated in many human tumors. In this study we report an adult male patient with NS who underwent both transsphenoidal and transcranial pituitary surgeries, conventional and stereotaxic radiotherapy and brachytherapy. Despite of the efforts to control tumor mass and growth, this macroadenoma displayed relentless growth and aggressive behavior. DNA extracted from the first two surgical samples, as well as DNA from peripheral blood leukocytes disclosed normal p53 sequence. DNA extracted from tumor samples obtained at surgeries performed after pituitary irradiation carried a somatic heterozygous mutation, consisting of a deletion of four cytosines between nucleotides 12,144-12,149 in exon 4 of the p53 gene. This frameshift mutation creates a stop codon in exon 4 excluding the expression of a functional protein from the defective allele. These data demonstrate a possible association between the P53 protein loss of function induced by radiotherapy and the aggressive course of the disease in this patient.
Appears in Collections:

Artigos e Materiais de Revistas Científicas - FM/MCM
Departamento de Clínica Médica - FM/MCM

Artigos e Materiais de Revistas Científicas - FM/MPT
Departamento de Patologia - FM/MPT

Artigos e Materiais de Revistas Científicas - HC/ICESP
Instituto do Câncer do Estado de São Paulo - HC/ICESP

Artigos e Materiais de Revistas Científicas - HC/ICHC
Instituto Central - HC/ICHC

Artigos e Materiais de Revistas Científicas - LIM/14
LIM/14 - Laboratório de Investigação em Patologia Hepática

Artigos e Materiais de Revistas Científicas - LIM/22
LIM/22 - Laboratório de Patolologia Cardiovascular

Artigos e Materiais de Revistas Científicas - LIM/42
LIM/42 - Laboratório de Hormônios e Genética Molecular

Files in This Item:
File Description SizeFormat 
  Restricted Access
publishedVersion (English)1.86 MBAdobe PDFView/Open Request a copy

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.