GENOMIC IMPRINTING OF THE HUMAN SEROTONIN-RECEPTOR (HTR2) GENE INVOLVED IN DEVELOPMENT OF RETINOBLASTOMA

Epidemiological and genetic studies of retinoblastoma (RB) suggested t hat imprinted genes might be genetically linked to the RB gene. In thi s study, we found that the human serotonin-receptor, HTR2, gene, which had been mapped nearby the RB gene on chromosome 13, was expressed on ly in human fibroblasts with a maternal allele and not in cells withou t a maternal allele. The 5' genomic region of the human HTR2 gene was cloned by PCR-mediated method. Only the 5' region of the gene was meth ylated in cells with the maternal gene, and it was not methylated in c ells without the maternal gene. A polymorphism of PvuII site of the ge ne was also found and useful for the segregation analysis in a family of a RB patient and for analysis of loss of heterozygosity on chromoso me 13 in tumor and its parental origin. These results suggest that the human HTR2 gene might be affected by genomic imprinting and that excl usive expression of the maternal HTR2 gene may be associated with the delayed occurrence of RB, which had lost the maternal chromosome 13.