Abstract
The purpose of this study was to identify novel areas of genomic copy number change associated with transformation from follicular lymphoma (FL) to diffuse large B cell lymphoma (DLBL). DNA was extracted from tumour cells micro-dissected from paraffin- embedded tissue sections in 24 patients with FL and subsequent transformation to DLBL and 18 patients with de novo DLBL. Tumour DNA was compared to reference DNA using comparative genomic hybridization. Abnormalities common to all 3 groups were gains on chromosomes 4q, 5q, 7q, 11q and X and losses on 3p, 8p and 10q. Copy number changes seen in both transformed and de novo DLBL and not seen in FL were gains on 2p and losses on 1q, 15q and Xq. Gains on 2q, 6p, 7p and 17q and losses on 5p and 8q were specific to transformed DLBL cases. Gain on 12q12-14 was found in 52% of the transformed DLBL cases and was never seen in its follicular counterpart. Patterns of genomic copy number change associated with specific clinical events in NHL have been demonstrated and suggest that gains on 2q, 6p, 7p, 12q and 17q and losses on 5p and 8q may be important in the transformation from low to high-grade disease. © 2001 Cancer Research Campaign
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Acker B, Hoppe RT, Colby TV, Cox RS, Kaplan HS and Rosenberg SA (1983) Histologic conversion in the non-Hodgkin’s lymphomas. J Clin Oncol 1: 11–16
Armitage JO (1993) Treatment of non-Hodgkin’s lymphoma. N Eng J Med 328: 1023–1030
Avet-Loisseau H, Mellerin MP, Moreau A, Gaillard F, Vigier M, Harousseau JL and Bataille N (1996) The usefulness of comparative genomic hybridization for analysis of genomic abnormalities in follicular lymphoma: A preliminary study about 28 patients. Br J Haematol 93: 279 (abstr)
Avet-Loiseau H, Vigier M, Moreau A, Mellerin MP, Gaillard F, Harousseau JL, Battaille R and Milpied N (1997) Comparative genomic hybridization detects genomic abnormalities in 80% of follicular lymphomas. Br J Haematol 97: 119–122
Bastion Y, Sebban C, Berger F, Felman P, Salles G, Dumontet C, Bryon PA and Coiffier B (1998) Incidence, predictive factors, and outcome of lymphoma transformation in follicular lymphoma patients. J Clin Oncol 15: 1587–1594
Bentz M, Werner CA, Dohner H, Joos S, Barth TFE, Siebert R, Schroder M, Stilgenbauer S, Fischer K, Moller P and Lichter P (1996) High incidence of chromosomal imbalances and gene amplifications in the classicle follicular variant of follicle centre lymphoma. Blood 88: 1437–1444
Dierlamm J, Rosenberg C, Stul M, Pittaluga S, Michaux L, Wiodarska I, Verhoef G, Thomas J, Janssen M, Bakker-Schut T, Zeller W, Cassiman JJ, Raap A, De Wolf-Peeters C, Van Den Berghe H and Hagemeijer A (1996) Chromosomal gains and losses in marginal zone B-cell lymphoma detected by comparative genomic hybridization. Blood 88: 378a (abstr)
Elkahloun AG, Bittner M, Hoskins K and Gemmill R Meltzer (1996) Molecular cytogenetic characterisation and physical mapping of 12q13-15 amplification in human cancers. Genes Chromosom Cancer 17: 205–214
Fifth International Workshop on Chromosomes in Leukemia-Lymphoma (1987) Correlation of chromosomal abnormalities with histologic and immunologic characteristics in non-Hodgkin’s lymphoma and adult T-cell leukemia-lymphoma. Blood 69: 97–102
Finnegan MCM, Goepel JR, Royds J, Hancock BW and Goyns MH (1994) Elevated levels of MDM-2 and p53 expression are associated with high grade non-Hodgkin’s lymphomas. Cancer Lett 86: 215–221
Goodacre A, Ford R and Andreeff M (1994) Comparative genomic hybridization resolves karyotypic heterogeneity in high grade non-Hodgkin’s lymphoma. Blood 84: 143a (abstr)
Goyns M, Hammond DW, Harrison CJ, Menasce LP, Ross F and Hancock BW (1993) Structural abnormalities of the X chromosome in non-Hodgkin’s lymphomas. Leukemia 7: 848–852
Hammond DW, Goepel JR, Aitken M, Hancock BW, Potter AM and Goyns MH (1992) Cytogenetic analysis of a United Kingdom series of non-Hodgkin’s lymphomas. Cancer Genet Cytogenet 61: 31–38
Harris NL, Jaffe ES, Stein H, Banks PM, Chan JKC, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC, Grogan TM, Isaacson PG, Knowles DM, Mason DY, Muller-Hermelink HK, Pileri SA, Piris MA, Ralfkiaer E and Warnke RA (1994) A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84: 1361–1392
Horning SJ and Rosenberg SA (1984) The natural history of initially untreated low-grade non-Hodgkin’s lymphomas. N Eng J Med 311: 1471–1475
Houldsworth J, Mathew S, Rao PH, Dyomina K, Louie DC, Parsa N, Offit K and Chaganti RSK (1996) REL proto-oncogene is frequently amplified in extranodal diffuse large cell lymphoma. Blood 87: 25–29
Joos S, Otano-Joos MI, Ziegler S, Bruderlein S, Du Manoir S, Bentz M, Moller P and Lichter P (1996) Primary mediastinal (thymic) B-cell lymphoma is characterized by gains of chromosomal material including 9p and amplification of the REL gene. Blood 87: 1571–1578
Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F and Pinkel D (1992) Comparative genomic hybridisation for molecular cytogenetic analysis of solid tumours. Science 258: 818–821
Kallioniemi OP, Kallioniemi A, Piper J, Isola J, Waldman FM, Gray JW and Pinkel D (1994) Optimizing comparative genomic hybridization for analysis of DNA sequence copy number change in solid tumours. Genes Chromosom Cancer 10: 231–243
Khatib ZA, Matsushime H, Valentine M, Shapiro DN, Sherr CJ and Look AT (1993) Coamplification of the CDK4 gene with MDM2 and GLI1 in human sarcomas. Cancer Res 53: 5535–5541
Knuutila S, Björkqvist AM, Autio K, Tarkkanen M, Wolf M, Monni O, Szymanska J, Larramendy ML, Tapper J, Pere H, El-Rifai W, Hemmer S, Wasenius VM, Vidgren V and Zhu Y (1998) DNA copy number amplifications in human neoplasms. Review of comparative genomic hybridisation studies. Am J Pathol 152: 1107–1123
Lee JT, Innes DJ and Williams ME (1989) Sequential bcl-2 and c-myc oncogene rearrangements associated with clinical transformation of non-Hodgkin’s lymphoma. J Clin Invest 84: 1454–1459
Lo Coco F, Gaidano G, Louie DC, Offit K, Chaganti RS and Dalla-Favera R (1993) p53 mutations are associated with histologic transformation of follicular lymphoma. Blood 82: 2289–2295
Monni O, Joensuu H, Franssila K and Knuutila S (1996) DNA copy number changes in diffuse large B-cell lymphoma-comparative genomic hybridization study. Blood 87: 5269–5278
Offit K, Jhanwar SC, Ladanyi M, Jilippa DA and Chaganti SRK (1991) Cytogenetic analysis of 434 consecutively ascertained specimens of non-Hodgkin’s lymphoma: correlations between recurrent aberrations, histology and exposure to cytotoxic treatment. Genes Chrom Cancer 3: 189–201
Rao PH, Houldsworth J, Dyomina K, Parsa NZ, Cigudosa JC, Louie DC, Popplewell L, Offit K, Jhanwar SC and Chaganti RSK (1998) Chromosomal and gene amplification in diffuse large B cell lymphoma. Blood 92: 234–240
Reifenberger G, Reifenberger J, Ichimura K, Meltzer PS and Collins VP (1994) Amplification of multiple genes from chromosomal region 12q13–14 in human malignant gliomas: Preliminary mapping of the amplicons shows preferential involvement of CDK4, SAS, and MDM2. Cancer Res 54: 4299–4303
Riou G, Barrois M, Prost S, Terrier M, Theodore C and Levine AJ (1995) The p53 and MDM2 genes in human testicular germ cell tumours. Mol Carcinogen 12: 124–131
Sander C, Yano T, Clark HM, Harris C, Longo DL, Jaffe ES and Raffeld M (1993) p53 mutation is associated with progression in follicular lymphomas. Blood 82: 1994–2004
Sattler HP, Zimmer E, Wellman A, Rohde V and Wullich B (1999) Amplification of growth regulatory genes on 3q25–q27 in human prostate cancer. Proc AACR 40: 542 (abstr)
Werner CA, Dohhner H, Joos S, Trumper LH, Baudis M, Barth TFE, Ott G, Moller P, Lichter P and Bentz M (1997) High level DNA amplifications are common genetic aberrations in B-cell neoplasms. Am J Pathol 151: 335–342
Wolf M, Aaltonen LA, Szymanska J, Tarkkanen M, Blomqvist C, Berner JM, Myklebost O and Knuutila S (1997) Complexity of 12q13–22 amplicon in liposarcoma: microsatellite repeat analysis. Genes Chrom Cancer 18: 66–70
Xu Q and Reed JC (1998) Bax inhibitor-1, a mammalian apoptosis suppressor identified by functional screening in yeast. Molec Cell 1: 337–346
Yano T, Jaffe ES, Longo DL and Raffeld M (1992) MYC rearrangements in histologically progressed follicular lymphomas. Blood 80: 758–767
Yunis JJ, Frizzera MM, Oken J, McKenna A, Theologides A and Arsnesen M (1987) Multiple recurrent genomic defects in follicular lymphoma. A possible model for cancer. N Eng J Med 316: 79–84
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Hough, R., Goepel, J., Alcock, H. et al. Copy number gain at 12q12-14 may be important in the transformation from follicular lymphoma to diffuse large B cell lymphoma. Br J Cancer 84, 499–503 (2001). https://doi.org/10.1054/bjoc.2000.1638
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1054/bjoc.2000.1638
Keywords
This article is cited by
-
Genome-wide detection of recurring sites of uniparental disomy in follicular and transformed follicular lymphoma
Leukemia (2007)
-
Genomic imbalances during transformation from follicular lymphoma to diffuse large B-cell lymphoma
Modern Pathology (2007)
-
Non-Hodgkin lymphoma with t(14;18): clonal evolution patterns and cytogenetic–pathologic–clinical correlations
Journal of Cancer Research and Clinical Oncology (2007)
-
Clinical and molecular prognostic factors in follicular lymphoma
Current Oncology Reports (2006)
-
A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma
Leukemia (2005)
