Loss of heterozygosity at the mannose 6-phosphate/insulin-like growth factor 2 receptor locus: a frequent but late event in adrenocortical tumorigenesis.
OBJECTIVE
Recent studies have pointed to the role of the IGF system in adrenocortical tumorigenesis. The IGF-II gene is overexpressed in malignant adrenocortical tumors and its proliferative effects are mediated by the type-1 IGF receptor (IGF1R). The mannose 6-phosphate/IGF2 receptor (M6P/IGF2R) plays a key role in regulating cell growth, by ensuring the clearance and inactivation of IGF-II and facilitating activation of the growth inhibitor, transforming growth factor beta (TGFbeta1). The M6P/IGF2R has been implicated as a tumor suppressor gene in various human tumors.


METHODS
The purpose of this study was to determine if the M6P/IGF2R is involved in adrenal tumorigenesis. Two polymorphisms in the 3' untranslated region of M6P/IGF2R were used to screen a large series of 76 sporadic adrenocortical tumors for loss of heterozygosity (LOH) by PCR amplification of DNA. Tumors were classified into three groups based on pathological features: benign tumors (n=25), suspect tumors (n=22) and malignant tumors (n=29).


RESULTS
LOH at the M6P/IGF2R locus was detected in 15 of 57 (26%) informative tumors and was more frequent in malignant tumors (58%) than in benign and suspect tumors (9 and 13% respectively).


CONCLUSIONS
These findings provide evidence that LOH at the M6P/IGF2R locus is a frequent event in adrenocortical tumors and support the hypothesis that it may function as a tumor suppressor gene in adrenocortical tumorigenesis.
Leboulleux
S
S
Laboratoire d'Explorations Fonctionnelles Endocriniennes, Hôpital Trousseau, AP-HP, 26 Avenue Arnold Netter, 75012 Paris, France.
Gaston
V
V
Boulle
N
N
Le Bouc
Y
Y
Gicquel
C
C
D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D005260:Female; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D019656:Loss of Heterozygosity; D008297:Male; D008360:Mannosephosphates / Q000235:genetics*; D008875:Middle Aged; D017451:Receptors, Somatomedin / Q000235:genetics*; D013997:Time Factors
D008360:Mannosephosphates; D017451:Receptors, Somatomedin; C027693:mannose-6-phosphate; D007335:Insulin-Like Growth Factor II