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 adr enocortical tumorigenesis. The IGF-II gene is overexpressed in malignant ad renocortical tumors and its proliferative effects are mediated by the type- 1 IGF receptor (IGF1R). The mannose 6-phosphate/IGF2 receptor (M6P/IGF2R) p lays a key role in regulating cell growth, by ensuring the clearance and in activation of IGF-II and facilitating activation of the growth inhibitor. t ransforming growth factor beta (TGF beta1). The M6P/IGF2R has been implicat ed as a tumor suppressor gene in various human tumors. Methods: The purpose of this study was to determine if the M6P/IGF2R is inv olved in adrenal tumorigenesis. Two polymorphisms in the 3' untranslated re gion of M6P/IGF2R were used to screen a large series of 76 sporadic adrenoc ortical 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 = 2 9). Results: LOH at the M6P/IGF2R locus was detected in 15 of 57 (26%) informat ive tumors and was more frequent in malignant tumors (58%) than in benign a nd suspect tumors (9 and 13% respectively). Conclusion: These findings provide evidence that LOH at the M6P/IGF2R locus is a frequent event in adrenocortical tumors and support the hypothesis th at it may function as a tumor suppressor gene in adrenocortical tumorigenes is.