title: Genome-wide copy-number analyses reveal genomic abnormalities involved in transformation of follicular lymphoma.
abstract: Follicular lymphoma (FL), the second most common type of non-Hodgkin lymphoma in the western world, is characterized by the t(14;18) translocation, which is present in up to 90% of cases. We studied 277 lymphoma samples (198 FL and 79 transformed FL [tFL]) using a single-nucleotide polymorphism array to identify the secondary chromosomal abnormalities that drive the development of FL and its transformation to diffuse large B-cell lymphoma. Common recurrent chromosomal abnormalities in FL included gains of 2, 5, 7, 6p, 8, 12, 17q, 18, 21, and X and losses on 6q and 17p. We also observed many frequent small abnormalities, including losses of 1p36.33-p36.31, 6q23.3-q24.1, and 10q23.1-q25.1 and gains of 2p16.1-p15, 8q24.13-q24.3, and 12q12-q13.13, and identified candidate genes that may be driving this selection. Recurrent abnormalities more frequent in tFL samples included gains of 3q27.3-q28 and chromosome 11 and losses of 9p21.3 and 15q. Four abnormalities, gain of X or Xp and losses of 6q23.2-24.1 or 6q13-15, predicted overall survival. Abnormalities associated with transformation of the disease likely impair immune surveillance, activate the nuclear factor-κB pathway, and deregulate p53 and B-cell transcription factors.
authors.affiliation: Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE;
authors.forename: Alyssa
authors.initials: A
authors.lastname: Bouska
authors.forename: Timothy W
authors.initials: TW
authors.lastname: McKeithan
authors.forename: Karen E
authors.initials: KE
authors.lastname: Deffenbacher
authors.forename: Cynthia
authors.initials: C
authors.lastname: Lachel
authors.forename: George W
authors.initials: GW
authors.lastname: Wright
authors.forename: Javeed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Smith
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.forename: Can
authors.initials: C
authors.lastname: Kucuk
authors.forename: Andrea
authors.initials: A
authors.lastname: Rinaldi
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoni
authors.forename: Jude
authors.initials: J
authors.lastname: Fitzgibbon
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.forename: Bhavana J
authors.initials: BJ
authors.lastname: Dave
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Rita M
authors.initials: RM
authors.lastname: Braziel
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Wing-Chung
authors.initials: WC
authors.lastname: Chan
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D015996:Survival Rate; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
references.citation: Clin Cancer Res. 2008 Nov 15;14(22):7180-7
references.pmid: 19010834
references.citation: Blood. 2012 May 10;119(19):4486-98
references.pmid: 22451425
references.citation: J Biol Chem. 2005 Aug 12;280(32):29233-41
references.pmid: 15951441
references.citation: Br J Haematol. 2010 Nov;151(3):221-31
references.pmid: 20813005
references.citation: Cancer Cell. 2012 Sep 11;22(3):359-72
references.pmid: 22975378
references.citation: Blood. 2008 Aug 1;112(3):644-51
references.pmid: 18487509
references.citation: J Pathol. 2013 Feb;229(3):430-40
references.pmid: 23165652
references.citation: J Clin Pathol. 2005 Jan;58(1):81-2
references.pmid: 15623489
references.citation: Cancer Res. 2011 Nov 1;71(21):6718-27
references.pmid: 21900401
references.citation: Br J Haematol. 2009 Aug;146(3):257-69
references.pmid: 19500100
references.citation: N Engl J Med. 2011 Dec 29;365(26):2497-506
references.pmid: 22150006
references.citation: Cancer Res. 2010 Nov 15;70(22):9166-74
references.pmid: 20884631
references.citation: Oncogene. 2011 Apr 7;30(14):1615-30
references.pmid: 21170083
references.citation: Nat Immunol. 2001 Oct;2(10):939-46
references.pmid: 11577348
references.citation: Cell Death Differ. 2004 Nov;11(11):1155-6
references.pmid: 15375384
references.citation: J Theor Biol. 2008 Nov 21;255(2):210-22
references.pmid: 18786548
references.citation: Cancer Cell. 2011 Dec 13;20(6):728-40
references.pmid: 22137796
references.citation: Leukemia. 2012 Mar;26(3):559-62
references.pmid: 21941365
references.citation: J Exp Med. 2012 Nov 19;209(12):2183-98
references.pmid: 23091163
references.citation: Blood. 2009 Mar 5;113(10):2298-301
references.pmid: 19141865
references.citation: PLoS One. 2011;6(9):e24504
references.pmid: 21915344
references.citation: Nature. 2010 Jan 7;463(7277):103-7
references.pmid: 20023629
references.citation: Oncogene. 2008 Jun 26;27(28):3912-22
references.pmid: 18264132
references.citation: J Clin Invest. 2012 Oct;122(10):3424-31
references.pmid: 23023713
references.citation: J Immunol. 2010 Sep 1;185(5):2730-6
references.pmid: 20660710
references.citation: Curr Opin Immunol. 1998 Jun;10(3):353-9
references.pmid: 9638373
references.citation: Am J Hum Genet. 2007 Jul;81(1):114-26
references.pmid: 17564968
references.citation: Blood. 2011 Nov 17;118(20):5550-8
references.pmid: 21960592
references.citation: Genes Chromosomes Cancer. 2010 Aug;49(8):669-81
references.pmid: 20544841
references.citation: Genes Chromosomes Cancer. 2004 Mar;39(3):195-204
references.pmid: 14732921
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13520-5
references.pmid: 18765795
references.citation: Nat Genet. 2011 Jul 31;43(9):830-7
references.pmid: 21804550
references.citation: Nature. 2012 Oct 4;490(7418):116-20
references.pmid: 22885699
references.citation: Genes Chromosomes Cancer. 2001 Apr;30(4):375-82
references.pmid: 11241790
references.citation: Clin Cancer Res. 2007 Aug 15;13(16):4777-85
references.pmid: 17699855
references.citation: Blood. 2011 Oct 6;118(14):3932-41
references.pmid: 21828135
references.citation: Cancer Res. 2008 Feb 1;68(3):808-14
references.pmid: 18245482
references.citation: Cancer Genet Cytogenet. 2002 Jun;135(2):103-9
references.pmid: 12127394
references.citation: Genes Dev. 2000 Jul 15;14(14):1810-23
references.pmid: 10898795
references.citation: J Theor Biol. 1993 Sep 7;164(1):37-64
references.pmid: 8264243
references.citation: J Exp Med. 2012 Dec 17;209(13):2455-65
references.pmid: 23166356
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15524-9
references.pmid: 12434020
references.citation: Cell. 2012 Aug 31;150(5):948-60
references.pmid: 22939622
references.citation: Biochem J. 2011 Nov 15;440(1):23-31
references.pmid: 21770894
references.citation: Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):21028-33
references.pmid: 23213261
references.citation: J Biol Chem. 2004 Jan 30;279(5):3151-9
references.pmid: 14607843
references.citation: Leukemia. 2007 Jul;21(7):1514-20
references.pmid: 17495976
references.citation: Genes Chromosomes Cancer. 2013 Aug;52(8):764-74
references.pmid: 23716461
references.citation: Crit Rev Oncol Hematol. 2013 May;86(2):97-103
references.pmid: 23266085
references.citation: Blood. 2009 Jan 1;113(1):137-48
references.pmid: 18703704
references.citation: Am J Clin Pathol. 2009 Oct;132(4):589-96
references.pmid: 19762537
references.citation: Nat Immunol. 2012 Nov;13(11):1083-91
references.pmid: 23001145
references.citation: Blood. 2002 Apr 1;99(7):2285-90
references.pmid: 11895757
references.citation: Bioinformatics. 2007 Mar 15;23(6):657-63
references.pmid: 17234643
references.citation: Cell. 2010 Nov 12;143(4):592-605
references.pmid: 21074050
references.citation: J Biol Chem. 2011 Jan 21;286(3):1675-82
references.pmid: 20947507