title: Mutation of p16, p21 or cyclin dependent kinase 4 is rare in acute lymphoblastic leukaemia.
abstract: Homozygous deletion of the p16 tumour suppressor gene (at frequencies ranging from 14% to 29%) have been implicated in the pathogenesis of acute lymphoblastic leukaemia (ALL) by several studies. We investigated the prevalence of this deletion in a group of 46 Arab patients with common ALL. Deletion of p16 was assessed in a multiplex PCR which amplified a 405 bp fragment from exon 2 of the p16 gene, and a 242 bp fragment of the ApoE lipoprotein gene which served as an internal control. Homozygous deletion of p16 in tumour cells could be readily detected in samples containing >75% blasts. Surprisingly, none of the cases in our study showed homozygous deletion of the p16 gene. We also investigated the possibility of other genetic alterations in the p16 gene or mutation in the p21 and CDK4 (not previously reported in ALL) genes which are part of the same signal transduction pathway. A heterozygous G --> A transition at nucleotide position 273 of the p16 gene was present in one patient, but did not result in an amino acid change. A C --> A transversion at codon 88 of the p21 gene, which results in replacement of a phenylalanine with a leucine at position 63, was detected in one patient. In another patient a G --> C transversion in exon 2 at codon 82 (5'-untranslated region of the CDK4 gene) was detected. Results of this study showed mutation of p16, p21 or CDK4 to be rare events in Arab ALL patients.
authors.affiliation: Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: M H
authors.initials: MH
authors.lastname: Qari
authors.forename: S H
authors.initials: SH
authors.lastname: Khalil
authors.forename: M
authors.initials: M
authors.lastname: Kambouris
authors.forename: B F
authors.initials: BF
authors.lastname: Meyer
mesh_terms: D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D016213:Cyclins / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004791:Enzyme Inhibitors; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D019942:Genes, p16 / Q000235:genetics; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D009692:Nucleic Acid Heteroduplexes; D018844:Cyclin-Dependent Kinases