title: CDKN2 (MTS1/p16INK4A) gene alterations in hematological malignancies.
abstract: Cyclin dependent kinases (CDKs) make complexes with cyclins, and regulate cell cycle progression by their serine/threonine kinase activities. CDK inhibitors (CDKIs) arrest the inappropriate progression of the cell cycle by combining with CDKs. Because the functional loss of CDKIs may permit unlimited cell growth, their disruptions are thought to be associated with tumorigenesis. Recently, one CDKI, p16, was found, and its gene, CDKN2 (MTS1/p16INK4A), was identified on chromosome 9p21. Intensive investigations of the CDKN2 gene in various tumors have shown that alterations frequently occur in this gene, thus suggesting that the CDKN2 gene is a tumor suppressor gene. In hematological malignancies, CDKN2 gene alterations may be limited to lymphoid malignancies, especially T-cell type acute lymphocytic leukemias, in which frequent chromosomal abnormalities in the 9p21 region have been reported. The CDKN2 gene is also inactivated in some patients with non-Hodgkin's lymphomas, adult T-cell leukemias, and lymphoid blastic crisis of chronic myelogenous leukemias. The main mechanism of CDKN2 gene inactivation is thought to be homozygous deletion, but point mutations may also inactivate it in some cases. The CDKN2 gene appears to be the major tumor suppressor gene on chromosome 9p21, and it is thought to be involved in the tumorigenesis of various lymphoid malignancies.
authors.affiliation: First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Uchida
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Hotta
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D017354:Point Mutation
chemical_list: D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16