title: Molecular characterization of 9p21 deletions shows a minimal common deleted region removing CDKN2A exon 1 and CDKN2B exon 2 in diffuse large B-cell lymphomas.
abstract: Diffuse large B cell lymphoma represent the most frequent subtype of non Hodgkin's lymphoma, accounting for 30-40% of cases. Several studies have shown that CDKN2A and CDKN2B deletions are frequent in these lymphomas. These genes encode the P14ARF, CDKN2A, and CDKN2B proteins which play a key role in the control of the G1/S transition of the cell cycle. Using array CGH and a quantitative multiplex PCR method, we have previously identified such deletions in 36% of cases at diagnosis. Using a walking strategy to approach the breakpoints of these deletions we could identify the breakpoints junction of thirteen deletions in 11 patients and of two unbalanced translocation leading to a loss of these genes. A minimal common deleted region of 22.4 kb containing exon 1β of CDKN2A encoding P14ARF and exon 2 of CDKN2B encoding CDKN2B was present in all cases but one. Analysis by quantitative RT PCR showed that the expression level of these genes was decreased in these patients as compared with non deleted cases and that this level was correlated with the deletion status of P14ARF, CDKN2A, and CDKN2B. Analysis of the breakpoint sequences showed that some of them were clustered within a few hundred base-pairs suggesting, even if we failed to identify any clear recombination prone sequences, that in these deletions the rearrangement results from non-random mechanisms.
authors.affiliation: INSERM U918, Groupe d'étude des Proliférations Lymphodes, Institut Fédératif de Recherches multidisciplinaires sur les Peptides 23 (IFRMP23), Rouen, France.
authors.forename: Suzan
authors.initials: S
authors.lastname: Guney
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertrand
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jardin
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruminy
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Kerckaert
authors.forename: Hervé
authors.initials: H
authors.lastname: Tilly
authors.forename: Christian
authors.initials: C
authors.lastname: Bastard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics* / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D014178:Translocation, Genetic
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16