Physical Mapping of Commonly Deleted Region on Chromosome 3p in Human Cancers Based on Radiation Hybrid (RH) Mapping

Hirokuni TAKANO[1]
Takashi KOHNO[1]
Hiroaki SHIMIZU[1]
Ryuya SHIMODA[1]
Naohito YAMAGUCH1[2]
Jun YOKOTA[1]

[1]Biol. Div.
[2]Epidemiol. Div., Natl. Cancer Centr. Res. Inst.


Abstract

Frequent allelic loss on the short arm of chromosome 3 in a variety of human cancers strongly suggests the presence of tumor suppressor gene in the region commonly deleted in these cancers. To isolate tumor suppressor gene at 3p21 which is one of the commonly deleted regions in lung and renal cell carcinomas, we developed a radiation hybrid (RH) mapping system to map and define the order of DNA markers for chromosome 3p (Genomics, 13: 705-712, 1992). By using a panel of 96 RHs that retain several sizes and portions of human chromosome 3p segments, we first mapped 24 DNA markers for chromosome 3p by the method proposed by Falk. We then mapped additional 84 DNA markers by the same method, and in total 51 DNA markers were mapped in the 3p21 region spanning approximately 5Mb on chromosome 3p. Chromosomal locations defined by RH mapping were in good agreement with those by either genetic linkage analysis or chromosomal in situ hybridization. Therefore, a physical map was further constructed by pulsed-field gel electrophoresis based on RH mapping data. Pairs of DNA markers with the d values of less then 0.04 were all mapped within 500kb in physical lengths. Those results suggest RH mapping data is useful to construct a physical map in a specific chromosomal region.