title: Alterations of CDKN2 gene structure in childhood acute lymphoblastic leukemia: mutations of CDKN2 are observed preferentially in T lineage.
abstract: We analyzed homozygous deletions and mutations of the CDKN2(p16(INK4A)/MTS1) gene, using polymerase chain reaction and Southern blot analysis, in 120 children with acute lymphoblastic leukemia (ALL). Homozygous deletion was found in 17 of 89 (19%) precursor B-ALL patients, in 11 of 24 (46%) T-ALL patients, and in 0 of 7 other phenotype ALL patients. After excluding 28 (23%) patients who showed a homozygous deletion of CDKN2, we found that three patients (3%) had mutation at exon 2 of CDKN2 using PCR-SSCP and sequencing strategy. One had a CGA to TGA nonsense mutation (Arg to stop) at codon 72, one had a 1-bp deletion at codon 117, and the third had a 2-bp deletion at codon 70, resulting in frameshifts in the two latter patients. All three of these patients were T phenotype ALL, and the incidence of mutation in the 24 T-ALL patients examined was 13%. In contrast, no mutation was detected in the remaining patients with precursor-B or other type ALL (0/96). Our results suggest that mutational inactivation of the CDKN2 gene may contribute to the leukemogenic growth, especially in some patients with T-ALL.
authors.affiliation: Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakao
authors.forename: S
authors.initials: S
authors.lastname: Yokota
authors.forename: H
authors.initials: H
authors.lastname: Kaneko
authors.forename: T
authors.initials: T
authors.lastname: Seriu
authors.forename: S
authors.initials: S
authors.lastname: Koizumi
authors.forename: Y
authors.initials: Y
authors.lastname: Takaue
authors.forename: T
authors.initials: T
authors.lastname: Fujimoto
authors.forename: S
authors.initials: S
authors.lastname: Misawa
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D019070:Cell Lineage; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D017353:Gene Deletion; D015973:Gene Expression Regulation, Leukemic; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D047428:Protein Kinase Inhibitors
chemical_list: D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D047428:Protein Kinase Inhibitors