PURPOSE: Follicular lymphoma (FL) constitutes the second most common non-Hodgkin's lymphoma in the Western world. The clinical course is variable and only in part explained by known tumor-intrinsic or -extrinsic factors. FL carries the hallmark chromosomal translocation t(14;18), deregulating the expression of Bcl-2, but this is not sufficient to explain either FL biology or clinical behavior. EXPERIMENTAL DESIGN: We have employed high-density genomic profiling technology using the Affymetrix 50K-XbaI oligonucleotide single nucleotide polymorphism-chip platform to interrogate the genomes of 58 fluorescence-activated cell-sorted (FACS) FL specimens for chromosomal copy number changes and 46 specimens for loss of heterozygosity (LOH). RESULTS: We report (a) previously unknown high-frequency copy-neutral LOH (uniparental disomy) in FL on chromosomes 1p (approximately 50%) and 6p (approximately 30%); (b) that del6q is complex, as reported, with at least two regions of minimal common loss at 6q13-15 and 6q23-24, and that in addition, approximately 8% of FL specimens contain a homozygous deletion at 6q23.3-24.1 that spans the negative NFkappaB regulator A20 and the p53 apoptosis effector PERP; (c) that combined analysis of chromosome 17p for LOH, copy number, and p53 mutations shows that most p53 mutations in FL do not involve del17p. Finally, we map high-frequency LOH with and without copy loss on chromosomes 9p, 10q, and 16p and genomic gains on 2p15-16 and 8q24.22-24.3. CONCLUSIONS: This comprehensive description of the pathologic anatomy of the FL genome uncovers novel genetic lesions and should aid with identification of genes relevant to FL biology and clinical behavior.
PURPOSE:Follicular lymphoma (FL) constitutes the second most common non-Hodgkin's lymphoma in the Western world. The clinical course is variable and only in part explained by known tumor-intrinsic or -extrinsic factors. FL carries the hallmark chromosomal translocation t(14;18), deregulating the expression of Bcl-2, but this is not sufficient to explain either FL biology or clinical behavior. EXPERIMENTAL DESIGN: We have employed high-density genomic profiling technology using the Affymetrix 50K-XbaI oligonucleotide single nucleotide polymorphism-chip platform to interrogate the genomes of 58 fluorescence-activated cell-sorted (FACS) FL specimens for chromosomal copy number changes and 46 specimens for loss of heterozygosity (LOH). RESULTS: We report (a) previously unknown high-frequency copy-neutral LOH (uniparental disomy) in FL on chromosomes 1p (approximately 50%) and 6p (approximately 30%); (b) that del6q is complex, as reported, with at least two regions of minimal common loss at 6q13-15 and 6q23-24, and that in addition, approximately 8% of FL specimens contain a homozygous deletion at 6q23.3-24.1 that spans the negative NFkappaB regulator A20 and the p53 apoptosis effector PERP; (c) that combined analysis of chromosome 17p for LOH, copy number, and p53 mutations shows that most p53 mutations in FL do not involve del17p. Finally, we map high-frequency LOH with and without copy loss on chromosomes 9p, 10q, and 16p and genomic gains on 2p15-16 and 8q24.22-24.3. CONCLUSIONS: This comprehensive description of the pathologic anatomy of the FL genome uncovers novel genetic lesions and should aid with identification of genes relevant to FL biology and clinical behavior.
Authors: Brian Parkin; Peter Ouillette; Yin Wang; Yan Liu; Whitney Wright; Diane Roulston; Anjali Purkayastha; Amanda Dressel; Judith Karp; Paula Bockenstedt; Ammar Al-Zoubi; Moshe Talpaz; Lisa Kujawski; Yang Liu; Kerby Shedden; Sajid Shakhan; Cheng Li; Harry Erba; Sami N Malek Journal: Clin Cancer Res Date: 2010-05-26 Impact factor: 12.531
Authors: Huferesh K Darbary; Smitha S Dutt; Sheila J Sait; Norma J Nowak; Roy E Heinaman; Daniel L Stoler; Garth R Anderson Journal: Cancer Genet Cytogenet Date: 2009-03
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Authors: Peter Ouillette; Kamlai Saiya-Cork; Erlene Seymour; Cheng Li; Kerby Shedden; Sami N Malek Journal: Clin Cancer Res Date: 2013-04-25 Impact factor: 12.531
Authors: Hongxiu Li; Mark S Kaminski; Yifeng Li; Mehmet Yildiz; Peter Ouillette; Siân Jones; Heather Fox; Kathryn Jacobi; Kamlai Saiya-Cork; Dale Bixby; Daniel Lebovic; Diane Roulston; Kerby Shedden; Michael Sabel; Lawrence Marentette; Vincent Cimmino; Alfred E Chang; Sami N Malek Journal: Blood Date: 2014-01-16 Impact factor: 22.113
Authors: Michael Boice; Darin Salloum; Frederic Mourcin; Viraj Sanghvi; Rada Amin; Elisa Oricchio; Man Jiang; Anja Mottok; Nicolas Denis-Lagache; Giovanni Ciriello; Wayne Tam; Julie Teruya-Feldstein; Elisa de Stanchina; Wing C Chan; Sami N Malek; Daisuke Ennishi; Renier J Brentjens; Randy D Gascoyne; Michel Cogné; Karin Tarte; Hans-Guido Wendel Journal: Cell Date: 2016-09-29 Impact factor: 41.582