title: P16INK4A gene homozygous deletions in human acute leukaemias with alterations of chromosome 9.
abstract: Acute leukaemias are characterized by nonrandom chromosomal aberrations which are often strictly related to the inactivation of tumour suppressor genes (TSGs). Alterations at the short arm of chromosome 9 have been reported in a remarkable percentage of acute lymphoblastic leukaemias (ALL) and have been suggested to cause the loss of activity of the putative TSG, p16INK4A (MTS1/CDKN2) gene. In order to evaluate the correlation between this gene inactivation and visible cytogenetic abnormalities, we have investigated p16INK4A homozygous gene deletions in 10 paediatric acute leukaemias of different cell lineages which demonstrated karyotype aberrations involving chromosome 9. Moreover, the dimension of the genetic alteration was evaluated by studying the loss of heterozygosity of two highly polymorphic markers of chromosome 9p, namely alpha-interferon (IFNA) and D9S104, and the deletion of 5'-methylthioadenosine phosphorylase (MTAPase) gene. Finally, the deletion of a gene belonging to p16INK4A family, the p18 gene, was analysed in these acute leukaemias. Our results demonstrated that: (1) the biallelic loss of p16INK4A gene is strictly related to a specific immunophenotype, namely ALL of T-cell lineage; (ii) no significant correlation exists between alterations at chromosome 9p level and the homozygous deletions of p16INK4A gene; and (iii) p18 gene was not deleted in the examined cases. These findings suggest a possible correlation between the T-lymphocyte phenotype and the expression of p16INK4A gene. Moreover, the absence of MTAPase activity seems to be a valuable marker of p16INK4A gene inactivation, thus indicating that the deleted chromosomal area on 9p21 very frequently involves the MTAPase gene.
authors.affiliation: Dipartimento di Biomedicina dell'Età Evolutiva, Università di Bari, Italy.
authors.forename: M F
authors.initials: MF
authors.lastname: Faienza
authors.forename: F
authors.initials: F
authors.lastname: della Ragione
authors.forename: G
authors.initials: G
authors.lastname: Basso
authors.forename: B
authors.initials: B
authors.lastname: Coppola
authors.forename: E
authors.initials: E
authors.lastname: Miraglia del Giudice
authors.forename: F
authors.initials: F
authors.lastname: Schettini
authors.forename: A
authors.initials: A
authors.lastname: Iolascon
mesh_terms: D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002899:Chromosomes, Human, Pair 9; D005260:Female; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics
chemical_list: D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase