Document Detail

Germline mutations of AIP gene in somatotropinomas resistant to somatostatin analogues.
MedLine Citation:
PMID:  23038625     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Most cases of familial isolated pituitary adenomas with mutated aryl hydrocarbon receptor-interacting protein (AIP:HGNC:358) gene develop somatotropinomas. They are characterised by an aggressive clinical phenotype including early age at diagnosis, large tumours and frequent invasiveness. There is little information on AIP gene mutations' prevalence in isolated somatotropinomas characterised by poor response to somatostatin analogue treatment. The aim of this study was to investigate the prevalence of AIP mutations in non-familial cases of somatotropinomas with poor response to conventional treatment.
DESIGN AND METHODS: Fifty patients with acromegaly (22 males/28 females, age 51±18 years) and 60 controls were included in this study performed at eight University Hospitals in Spain. None had family history of pituitary adenomas or other endocrine tumors. All patients failed to respond to conventional treatment including surgery and somatostatin analogues. Some patients received adjuvant radiotherapy and most cases required pegvisomant (PEG) treatment for normalisation of IGF1. AIP analysis was performed in DNA extracted from peripheral leucocytes, using standardised PCR protocol in which the coding regions of exons 1, 2, 3, 4, 5 and 6 were amplified. Possible deletions/duplications were studied using multiplex ligation-dependent probe amplification.
RESULTS: SEQUENCE CHANGES OF POTENTIAL DIFFERENT SIGNIFICANCE THAT COULD BE CONSIDERED AS MUTATIONS OR VARIATIONS OF UNKNOWN SIGNIFICANCE (VUS) OF THE AIP GENE WERE FOUND IN FOUR PATIENTS (8%). IN TWO CASES, TWO DIFFERENT MUTATIONS PREVIOUSLY DESCRIBED WERE FOUND: p.Arg9Gln and p.Phe269Phe. Two other VUS were also found: c.787+24C>T in intron 5 and c.100-18C>T in intron 1. Age at diagnosis ranged from 21 to 50 years old, and in all patients, the tumor was a macroadenoma depicting IGF1 normalisation under PEG treatment.
CONCLUSIONS: AIP germline mutations show a low, but non-negligible, prevalence in non-familial acromegaly patients with tumors resistant to treatment with somatostatin analogues.
Josep Oriola; Tomás Lucas; Irene Halperin; Mireia Mora; Ma José Perales; Cristina Alvarez-Escolá; de Miguel-Novoa Paz; Gonzalo Díaz Soto; Isabel Salinas; María Teresa Julián; Izaskun Olaizola; Ignacio Bernabeu; Mónica Marazuela; Manuel Puig-Domingo
Related Documents :
1921315 - Genetic variation within and between lines of diabetes-prone and non-diabetes-prone bb ...
8010535 - Conformation polymorphisms and targeted marker development.
24680725 - Treatment-resistant schizophrenia and dat and sert polymorphisms.
24516315 - Imatinib mesylate resistance and mutations: an indian experience.
23261845 - The amino acid substitutions rtp177g and rtf249a in the reverse transcriptase domain of...
12209585 - Vegf isoforms and mutations in human colorectal cancer.
Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't     Date:  2012-12-10
Journal Detail:
Title:  European journal of endocrinology / European Federation of Endocrine Societies     Volume:  168     ISSN:  1479-683X     ISO Abbreviation:  Eur. J. Endocrinol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-11     Completed Date:  2013-02-04     Revised Date:  2013-05-08    
Medline Journal Info:
Nlm Unique ID:  9423848     Medline TA:  Eur J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  9-13     Citation Subset:  IM    
Hospital Universitari Germans Trias i Pujol, Carretera de Canyet, Badalona, Spain.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Acromegaly / drug therapy,  genetics*
Adenoma / drug therapy,  genetics
Drug Resistance, Neoplasm
Germ-Line Mutation
Growth Hormone-Secreting Pituitary Adenoma / drug therapy,  genetics*
Intracellular Signaling Peptides and Proteins / genetics*
Middle Aged
Multiplex Polymerase Chain Reaction
Somatostatin / analogs & derivatives,  therapeutic use
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/aryl hydrocarbon receptor-interacting protein; 51110-01-1/Somatostatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Prednisolone reduces the ability of serum to activate the IGF1 receptor in vitro without affecting c...
Next Document:  Triple-layer reconstruction technique for large cribriform defects after endoscopic endonasal resect...