A new type of p16INK4/MTS1 gene transcript expressed in B-cell malignancies.
Chromosome band 9p21-22 is frequently altered by nonrandom abnormalities, mainly deletions, in hemopoietic malignancies of the lymphoid lineage. We have analysed a translocation t(9;14)(p21-p22;q11) in a B-cell type acute lymphoblastic leukemia. Location of the 14q11 breakpoint within the TCR-alpha/delta locus allowed the isolation of a fusion transcript composed of a 3' segment containing part of the constant region of the TCR-alpha gene and a 5' segment from chromosome 9, designated 0.18. This 0.18 segment was also part of cDNAs isolated from two tumoral B-cell lines (RPMI-8226, Raji). In both cases, 0.18 was juxtaposed 5' to a sequence corresponding to exons 2 and 3 of the p16INK4/MTS1 gene which is located on band 9p21-22. Unexpectedly, none of the two ATG codons found in 0.18 was in phase with that of the exons 2 and 3 of p16INK4/MTS1. Furthermore, in vitro translation product of a RPMI-8226 cDNA clone generated a product that was not immunoprecipitated by antibodies specific of the C-terminal end of the p16INK4/MTS1 protein. Evidence for similar transcripts in non tumoral lymphoid B cells (unstimulated peripheral blood lymphocytes (PBL) and lymphoblastoid cell lines) were obtained by using amplimers representative of the 0.18 segment and the p16INK4/MTS1 exon 2. Altogether, these data are consistent with the existence of a new type of p16INK4/MTS1 transcript whose significance is discussed.
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INSERM U-301, Institut de Génétique moléculaire and SDI no. 16954 I CNRS, Paris.
Bernard
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Della Valle
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Berger
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Larsen
C J
CJ
D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002648:Child; D002883:Chromosomes, Human, Pair 14; D002899:Chromosomes, Human, Pair 9; D003001:Cloning, Molecular; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015342:DNA Probes; D018076:DNA, Complementary; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D014178:Translocation, Genetic
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015342:DNA Probes; D018076:DNA, Complementary; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta