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 involved 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 hypermethylation of their promoters. In this work, we describe a simple-sequence length polymorphism located in mouse Chromosome (Chr) 4, between the Cdkn2B (p15 ^INK4b ) and Cdkn2A (p16 ^INK4a ) genes, only 700 bp downstream of the Cdkn2B locus. This DNA region was analyzed in different inbred strains showing a variable AC-repetitive DNA sequence. We used this microsatellite to detect loss of heterozygosity of the Cdkn2A and Cdkn2B loci in γ-irradiation-induced thymic lymphomas of C57BL/6J × RF/J F₁ hybrids. Using this specific marker, we were able to locate additional allelic losses not detected by other microsatellites. Since the allelic losses can be detected by a simple PCR amplification, this AC-repetitive sequence is specially useful as a genetic marker for these Cdkn2 genes and specifically for the p15 ^INK4b cell cycle inhibitor. Received: 27 August 1997 / Accepted: 13 November 1997