title: An AC-repeat adjacent to mouse Cdkn2B allows the detection of specific allelic losses in the p15INK4b and p16INK4a tumor suppressor genes.
abstract: The cyclin-dependent kinase inhibitors p15INK4b and p16INK4a 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 (p15INK4b) and Cdkn2A (p16INK4a) 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 gamma-irradiation-induced thymic lymphomas of C57BL/6J x 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 p15INK4b cell cycle inhibitor.
authors.affiliation: Department of Pathology, New York University Medical Center, New York 10016, USA.
authors.forename: M
authors.initials: M
authors.lastname: Malumbres
authors.forename: I
authors.initials: I
authors.lastname: Pérez de Castro
authors.forename: J
authors.initials: J
authors.lastname: Santos
authors.forename: R
authors.initials: R
authors.lastname: Pérez-Ollé
authors.forename: J
authors.initials: J
authors.lastname: Fernández-Piqueras
authors.forename: A
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D018900:Dinucleotide Repeats; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D047428:Protein Kinase Inhibitors; D025521:Tumor Suppressor Proteins
chemical_list: D002352:Carrier Proteins; C493968:Cdkn2b protein, mouse; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D047428:Protein Kinase Inhibitors; D025521:Tumor Suppressor Proteins