Molecular cytogenetic characterization of t(14;19)(q32;p13), a new recurrent translocation in B cell malignancies
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Translocations involving an immunoglobulin (IG) locus are a recurring theme in B cell neoplasia. The rearrangements lead to the joining of an IG gene with a (proto)oncogene, whereby the latter comes under the influence of transcription-stimulating sequences in the constitutively active IG locus resulting in deregulation of the oncogene and neoplastic growth. We present here three cases of B cell neoplasia that showed a t(14;19)(q32;p13) by karyotypic analysis. Detailed molecular cytogenetic characterization of the breakpoints on chromosomes 14 and 19 in the two cases from which extra material was available, demonstrated the involvement of the immunoglobulin heavy-chain (IGH@)-variable region on chromosome 14 in both and, in one case, that the breakpoint was within the BRD4 gene on chromosome 19. Against the background of what one knows about IGH@ involvement in lymphatic malignancies, it is difficult to envisage a fusion gene with qualitatively altered protein product as the crucial pathogenetic outcome of the translocation. In spite of the fact that we found BRD4 split by the t(14;19)(q32;p13) in one of the two informative cases, we cannot be sure that this was the pathogenetically relevant target gene. Other pathogenetic possibilities could be deregulation of the neighboring NOTCH3 and/or ABHD9 genes, located distal to BRD4 in 19p13.
KeywordsALL Large B cell lymphoma Cytogenetics t(14;19)(q32;p13) BRD4
This work was supported by grants from the Norwegian Cancer Society, COST Action B-19—Molecular cytogenetics of solid tumors—Short-term Scientific Mission programme, the Gunnar Nilsson’s Cancer Foundation, and The Swedish Children’s Cancer Foundation.
- 4.Bellavia D, Campese AF, Checquolo S, Balestri A, Biondi A, Cazzaniga G, Lendahl U, Fehling HJ, Hayday AC, Frati L, von Boehmer H, Gulino A, Screpanti I (2002) Combined expression of pTalpha and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis. Proc Natl Acad Sci USA 99:3788–3793PubMedCrossRefGoogle Scholar
- 7.Czepulkowski B, Gibbons B (2001) Cytogenetics in acute lymphoblastic leukemia. In: Rooney DE (ed) Human cytogenetics: malignancy and acquired abnormalities. Oxford University Press, Oxford, pp 57–85Google Scholar
- 12.French CA, Kutok JL, Faquin WC, Toretsky JA, Antonescu CR, Griffin CA, Nose V, Vargas SO, Moschovi M, Tzortzatou-Stathopoulou F, Miyoshi I, Perez-Atayde AR, Aster JC, Fletcher JA (2004) Midline carcinoma of children and young adults with NUT rearrangement. J Clin Oncol 22:4135–4139PubMedCrossRefGoogle Scholar
- 16.Heim S, Mitelman F (eds) (1995) Cancer cytogenetics. Wiley-Liss, New YorkGoogle Scholar
- 17.Shaffer LG, Tommerup N (eds) (2005) ISCN 2005: an international system for human cytogenetic nomenclature. S Karger, BaselGoogle Scholar
- 18.Kearny L, Hammomd DW (2001) Molecular cytogenetic technologies. In: Rooney DE (ed) Human cytogenetics—malignancy and acquired abnormalities. Oxford University Press, Oxford, pp 129–163Google Scholar
- 19.Martinez-Climent JA, Sanchez-Izquierdo D, Sarsotti E, Blesa D, Benet I, Climent J, Vizcarra E, Marugan I, Terol MJ, Sole F, Cigudosad JC, Siebert R, Dyer MJ, Garcia-Conde J (2003) Genomic abnormalities acquired in the blastic transformation of splenic marginal zone B-cell lymphoma. Leuk Lymphoma 44:459–464PubMedCrossRefGoogle Scholar
- 22.Mitelman, F., Johansson, B., Mertens, F. (2006) Mitelman database of chromosome aberrations in cancer. http://cgap.nci.nih.gov/Chromosomes/Mitelman
- 26.Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar