The Correlation Between Genetic Mutations Of Aryl Hydrocarbon Receptor Interacting Protein And Tumorigenesis Of Sporadic Pituitary Adenomas

ObjectiveThe aim of this study was to investigate the mutations of AIP gene in sporadic pituitary adenomas in Chinese population, and to analyze the correlation between mutations and tumorigenesis.MethodsOne hundred and fifty two patients with sporadic pituitary adenomas(88 males/64 females, age 45.8±13.5 years) were included in this study performed at Fuzhou General Hospital of Nanjing Command in China. None had family history of pituitary adenomas or other endocrine tumors. All patients received transsphenoidal surgery and were verified by pathology.AIP gene mutations analysis were performed in DNA extracted from tumor tissues, using polymerase chain reaction(PCR) protocol in which the coding regions of exons 1, 2, 3, 4, 5 and 6 were amplified. The mutations difference of AIP gene were compared to public database. Also, bioinformatics analysis was used to process the gene mutations data.ResultsSequence change of 682C>A(Q228K) in exon 5 that could be considered as mutations of the AIP gene were found in all 152 patients and the genotype was homozygous. The mutation occurred in 20 cases(13.2%), and located at 516 locus of Exon 4 sequence changed from C to T, and the base sequence was CT heterozygous genotype. A mutation was found in exon 6 at 920 locus(920A>G(Q307R)) in 41 cases(27%), and the genotype was homozygous.CT heterozygous mutation in exon 4 did not cause the sequence changes of encoding amino acid; but CT homozygous mutation 682C>A(Q228K) occurred in exon 5, resulted in the conversion of amino acids encoded by the glutamine lysine;and AG homozygous mutation 920A>G(Q307R) in exon 6 led to a change of amino acid glutamine to arginine.ConclusionThe mutations data and bioinformatics analysis results suggested that AIP gene mutations might be related to tumorigenesis of sporadic pituitary adenomas. These data may benefit further investigations of the pathogenesis of pituitary adenomas with AIP mutation. It revealed that AIP gene might be one of the possible pathogenic factor of pituitary adenomas, and AIP gene will be expected to become a new target point for early diagnosis and therapy of pituitary adenomas.