THE MANNOSE 6-PHOSPHATE INSULIN-LIKE GROWTH-FACTOR-2 RECEPTOR (M6P/IGF2R), A PUTATIVE BREAST-TUMOR SUPPRESSOR GENE/

Loss of heterozygosity (LOH) at the mannose 6-phosphate/insulin-like g rowth factor 2 receptor gene locus (M6P/IGF2R) on 6q26-27 has recently been demonstrated in approximately 30% of both invasive and in situ b reast cancers. LOH was coupled with somatic point mutations in the rem aining allele in several instances, leading to the proposition that M6 P/IGF2R is a tumor suppressor gene [1]. Somatic mutations in M6P/IGF2R have also been described in hepatoma [2] and gastrointestinal cancers with the replication error positive (RER+) phenotype [3]. These data indicate that M6P/IGF2R loss of function mutations may be involved in the pathogenesis of a wide spectrum of malignancies. Extensive data on the normal function of the M6P/IGF2R suggest that loss of M6P/IGF2R a ctivity may contribute to multiple aspects of tumor pathophysiology, i ncluding deregulated growth, apoptosis, angiogenesis and invasion.