AN AC-REPEAT ADJACENT TO MOUSE CDKN2B ALLOWS THE DETECTION OF SPECIFIC ALLELIC LOSSES IN THE P15(INK4B) AND P16(INK4A) TUMOR-SUPPRESSOR GENES

The cyclin-dependent kinase inhibitors p15(INK4b) and p16(INK4a) are i nvolved in the development of a wide range of human and murine tumors. These tumor suppressor genes are inactivated by deletions frequently associated to point mutations in the coding regions or hypermethylatio n of their promoters. In this work, we describe a simple-sequence leng th polymorphism located in mouse Chromosome (Chr) 4, between the Cdkn2 B (p15(INK4b)) and Cdkn2A (p16(INK4a)) genes, only 700 bp downstream o f the Cdkn2B locus. This DNA region was analyzed in different inbred s trains showing a variable AC-repetitive DNA sequence. We used this mic rosatellite to detect loss of heterozygosity of the Cdkn2A and Cdkn2B loci in gamma-irradiation-induced thymic lymphomas of C57BL/6J x RF/J F-1 hybrids. Using this specific marker, we were able to locate additi onal allelic losses not detected by other microsatellites. Since the a llelic losses can be detected by a simple PCR amplification, this AC-r epetitive sequence is specially useful as a genetic marker for these C dkn2 genes and specifically for the p15(INK4b) cell cycle inhibitor.