Kato M V, Shimizu T, Nagayoshi M, Kaneko A, Sasaki M S, Ikawa Y
Laboratory of Molecular Oncology, Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN).
Am J Hum Genet. 1996 Nov;59(5):1084-90.
Epidemiological and genetic studies of retinoblastoma (RB) suggested that imprinted genes might be genetically linked to the RB gene. In this study, we found that the human serotonin-receptor, HTR2, gene, which had been mapped nearby the RB gene on chromosome 13, was expressed only in human fibroblasts with a maternal allele and not in cells without 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 methylated in cells with the maternal gene, and it was not methylated in cells without the maternal gene. A polymorphism of PvuII site of the gene was also found and useful for the segregation analysis in a family of a RB patient and for analysis of loss of heterozygosity on chromosome 13 in tumor and its parental origin. These results suggest that the human HTR2 gene might be affected by genomic imprinting and that exclusive expression of the maternal HTR2 gene may be associated with the delayed occurrence of RB, which had lost the maternal chromosome 13.
视网膜母细胞瘤（RB）的流行病学和遗传学研究表明，印记基因可能与RB基因存在遗传联系。在本研究中，我们发现人类5-羟色胺受体基因HTR2定位于13号染色体上RB基因附近，且仅在携带母本等位基因的人成纤维细胞中表达，而在不携带母本等位基因的细胞中不表达。采用PCR介导的方法克隆了人类HTR2基因的5'基因组区域。在携带母本基因的细胞中，只有该基因的5'区域发生甲基化，而在不携带母本基因的细胞中则未发生甲基化。此外，还发现了该基因PvuII位点的多态性，这对于RB患者家系的分离分析以及肿瘤中13号染色体杂合性缺失及其亲本来源的分析非常有用。这些结果表明，人类HTR2基因可能受基因组印记影响，母本HTR2基因的特异性表达可能与RB的延迟发生有关，RB患者丢失了母本的13号染色体。
