Relationship between aryl hydrocarbon receptor interacting protein gene expression and clinical characteristics in human pituitary somatotrophinomas

Abstract

Objective To investigate the expression of aryl Hydrocarbon Receptor Interacting protein (AIP)gene mutations and relationship with clinical biochemical characteristics in human somatotropinomas. Methods From October 2009 to September 2012, 96 acromegaly or gigantism patients were diagnosed in a single pituitary center, with consistent treatment and follow-up. Genomic DNA from tumor tissues was extracted and sequenced. Clinical data were retrospectively analyzed. Results Overall,55 patients(57.3%)had one or more single base substitutions in AIP gene from their tumor tissues. Thirteen point mutations were detected in total, and 5 novel ones(c. 609C> G, c. 646- 38C> T, c. 646- 35C> T, c. 646- 34A> T and c. 692C> T)were firstly reported according to the National Center for Biotechnology Information(NCBI)single nucleotide polymorphism(SNP)database. Somatic AIPmut group showed characteristics as younger onset age(P<0.05), larger tumor diameter(P<0.05), higher invasiveness and aggressiveness(P< 0.05), and more prevalence in recurrent tumors(P<0.05),than the negative group. Conclusion Somatic AIP gene mutation screen may be clinically crucial for the substantial treatment and outcome prejudgement, as well as the follow- up duration and frequency. The treatment strategy for AIPmut patients remains stressful; in the meanwhile, the role of AIP gene in the pathogenesis of somatotropinomas await more investigation. Key words: Somatotrophinoma; Growth hormone; Aryl hydrocarbon receptor interacting protein gene; Mutation