Large genomic deletions in AIP in pituitary adenoma predisposition.
BACKGROUND
Germline mutations in AIP have been recently shown to cause pituitary adenoma predisposition (PAP). Subsequently, many intragenic germline mutations have been reported, both in familial and in sporadic settings.


OBJECTIVE
Our objective was to evaluate the possible contribution of large genomic germline AIP deletions, an important mutation type in tumor predisposition syndromes, in PAP.


METHODS
Here, we applied the multiplex ligation-dependent probe amplification assay to examine whether large genomic AIP or MEN1 alterations account for a subset of PAP cases.


METHODS
The study was performed on familial and sporadic pituitary adenoma cases of European origin, which had previously tested negative for germline AIP and MEN1 mutations by sequencing.


RESULTS
Two of 21 pituitary adenoma families (9.5%) were found to harbor an AIP deletion. No copy number changes were detected among 67 sporadic pituitary adenoma patients. No MEN1 deletions were found.


CONCLUSIONS
The present study shows that large genomic AIP deletions account for a subset of PAP. Therefore, in suspected PAP cases undergoing counseling and AIP genetic testing, multiplex ligation-dependent probe amplification could be considered if direct sequencing does not identify a mutation.
Georgitsi
Marianthi
M
Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland.
Heliövaara
Elina
E
Paschke
Ralf
R
Kumar
Ajith V K
AV
Tischkowitz
Marc
M
Vierimaa
Outi
O
Salmela
Pasi
P
Sane
Timo
T
De Menis
Ernesto
E
Cannavò
Salvatore
S
Gündogdu
Sadi
S
Lucassen
Anneke
A
Izatt
Louise
L
Aylwin
Simon
S
Bano
Gul
G
Hodgson
Shirley
S
Koch
Christian A
CA
Karhu
Auli
A
Aaltonen
Lauri A
LA
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics*
D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein