title: A novel bcl-1/JH breakpoint from a patient affected by mantle cell lymphoma extends the major translocation cluster.
abstract: Mantle cell lymphoma (MCL) is a B-lymphocytic malignancy frequently associated with the presence of the t(11;14) chromosomal translocation. By using a polymerase chain reaction (PCR) strategy to detect breakpoints within the major translocation cluster (MTC), an unexpectedly large product (about 1.1 kb by using first-round bcl-1/JH primers) has been identified in one out of 16 patients harbouring the t(11;14) translocation. Sequence analysis of the atypical PCR product, re-amplified and cloned with second-round primers, revealed a 459 bp portion corresponding exactly to the 3'-end segment of the MTC, followed by a sequence of 433 bp that lacked homology with any previously known sequence. PCR experiments using DNA from healthy donors identified that fragment as an extension of MTC fused, through a N-region of seven nucleotides, to the JH4 region of IgH gene. A computer-based search of the novel MTC portion aimed at detecting potential recombination motifs revealed the presence of several 4-bp sequences (5'-CCAG-3' or its complement 5'-CTGG-3'), one of them within seven nucleotides from the putative breakpoint, known to play a role in non-homologous recombination events at the Ig loci. The recognition of this novel breakpoint may have important implications for the diagnosis and detection of minimal residual disease in t(11;14)-positive lymphomas.
authors.affiliation: Clinical and Experimental Hematology Research Unit, Division of Experimental Oncology 2, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano I-33981, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Degan
authors.forename: Roberto
authors.initials: R
authors.lastname: Doliana
authors.forename: Annunziata
authors.initials: A
authors.lastname: Gloghini
authors.forename: Raffaele
authors.initials: R
authors.lastname: Di Francia
authors.forename: Donatella
authors.initials: D
authors.lastname: Aldinucci
authors.forename: Linda
authors.initials: L
authors.lastname: Mazzocut-Zecchin
authors.forename: Alfonso
authors.initials: A
authors.lastname: Colombatti
authors.forename: Vincenza
authors.initials: V
authors.lastname: Attadia
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
mesh_terms: D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D004273:DNA, Neoplasm / Q000235:genetics; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D019940:Genes, bcl-1 / Q000235:genetics; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction / Q000379:methods; D014178:Translocation, Genetic
chemical_list: D004273:DNA, Neoplasm