Aryl hydrocarbon receptor interacting protein variants in sporadic pituitary adenomas.
BACKGROUND
Proximal pathogenesis of pituitary tumors remains largely unclear. Recently, three heterozygous germline mutations were reported in the aryl hydrocarbon receptor interacting protein (AIP) gene in Finnish and Italian families with pituitary tumor predisposition and in Finnish patients harboring sporadic pituitary tumors.


OBJECTIVE
The objectives of this study were to examine the frequency of the three AIP germline mutations in U.S. patients harboring sporadic pituitary tumors and to correlate clinical features of pituitary tumors with these mutations, if they exist in these patients.


METHODS
Genomic DNA was extracted from lymphoblastoid cell lines established from patients with sporadic pituitary tumors. Three segments of the AIP gene that contain the reported mutation sites for Q14X, IVS3-1G>A, and R304X were amplified by PCR and sequenced.


METHODS
The study was conducted in a private nonprofit academic medical center.


METHODS
The subjects were 66 consecutive patients (including 52 with acromegaly or prolactinoma) participating in a pituitary tumor database who consented to genetic study.


METHODS
The main outcome measure was the prevalence of these specific germline mutations in affected individuals.


RESULTS
AIP mutations were not detected in the 66 patients. A synonymous polymorphism was found in a single patient with acromegaly.


CONCLUSIONS
The three specific AIP germline mutations do not play an important role in pathogenesis of sporadic pituitary tumors in U.S. patients.
Yu
Run
R
Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room 2015, Los Angeles, California 90048, USA.
Bonert
Vivien
V
Saporta
Inbar
I
Raffel
Leslie J
LJ
Melmed
Shlomo
S
D000236:Adenoma / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D014644:Genetic Variation; D018095:Germ-Line Mutation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000235:genetics*; D011506:Proteins / Q000235:genetics*
D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C103265:aryl hydrocarbon receptor-interacting protein