title: Molecular-cytogenetic characterization of non-Hodgkin's lymphoma with double and cryptic translocations of the immunoglobulin heavy chain gene.
abstract: The present study aimed to characterize the clinical and molecular-cytogenetic features of non-Hodgkin's lymphoma (NHL) with double translocation of the immunoglobulin heavy chain (IGH) gene. G-banding analysis, fluorescence in situ hybridization (FISH) with the IGH (Cgamma and VH) and oncogene (c-MYC, BCL1, BCL2, and BCL6) probes, and long-distance polymerase chain reaction (LD-PCR) were performed on 6 patients with B-cell lymphoma, one with angioimmunoblastic T-cell lymphoma, and one with acute lymphoblastic leukemia (ALL) with B-cell phenotype. G-banding analysis detected two different 14q32 translocations, t(14,18) and add (14)(q32) in a patient with ALL. Two distinct partners of double IGH translocation identified by FISH were as follows: c-MYC + BCL2 in 3 patients, c-MYC + BCL1 in 2, c-MYC + BCL6 in one, BCL2 + 9q22 in one, and 1q21 + 6q27 in one. Colocalization of BCL1 and c-MYC probes was demonstrated in a patient with mantle cell lymphoma. LD-PCR detected c-MYC/Cmu, c-MYC/Calpha and BCL6/Cmu, and c-MYC/Calpha fusion in each one patient. Seven of 8 patients showed high serum LDH. Central nervous system and leukemic involvement was observed in 5 and 6 patients, respectively. Median survival time of patients with c-MYC/IGH translocation was 9 months. The results defined a clinical subset of B-cell lymphoma/leukemia showing extremely poor prognosis. C-MYC/IGH translocation is possibly an evolutionary alteration following the primary IGH translocation with BCL1, BCL2, or BCL6. Furthermore, FISH identified one novel (9q22) and one cryptic chromosomal breakpoints (6q27) involved in IGH translocation.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kanda-Akano
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nomura
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Shigeo
authors.initials: S
authors.lastname: Horiike
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishida
authors.forename: Masami
authors.initials: M
authors.lastname: Nagai
authors.forename: Ikuo
authors.initials: I
authors.lastname: Miura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masao
authors.initials: M
authors.lastname: Seto
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Iida
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
mesh_terms: D000328:Adult; D000368:Aged; D002871:Chromosome Banding; D019938:Cyclin D1 / Q000235:genetics; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D016393:Lymphoma, B-Cell / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000235:genetics; D020522:Lymphoma, Mantle-Cell / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D019938:Cyclin D1