title: High-resolution copy number analysis of paired normal-tumor samples from diffuse large B cell lymphoma.
abstract: Copy number analysis can be useful for assessing prognosis in diffuse large B cell lymphoma (DLBCL). We analyzed copy number data from tumor samples of 60 patients diagnosed with DLBCL de novo and their matched normal samples. We detected 63 recurrent copy number alterations (CNAs), including 33 gains, 30 losses, and nine recurrent acquired copy number neutral loss of heterozygosity (CNN-LOH). Interestingly, 20 % of cases acquired CNN-LOH of 6p21 locus, which involves the HLA region. In normal cells, there were no CNAs but we observed CNN-LOH involving some key lymphoma regions such as 6p21 and 9p24.1 (5 %) and 17p13.1 (2.5 %) in DLBCL patients. Furthermore, a model with some specific CNA was able to predict the subtype of DLBCL, 1p36.32 and 10q23.31 losses being restricted to germinal center B cell-like (GCB) DLBCL. In contrast, 8p23.3 losses and 11q24.3 gains were strongly associated with the non-GCB subtype. A poor prognosis was associated with biallelic inactivation of TP53 or 18p11.32 losses, while prognosis was better in cases carrying 11q24.3 gains. In summary, CNA abnormalities identify specific DLBCL groups, and we describe CNN-LOH in germline cells from DLBCL patients that are associated with genes that probably play a key role in DLBCL development.
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.|Spanish Lymphoma/Autologous Bone Marrow Transplant Study Group (GELTAMO), Salamanca, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Sebastián
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.|Spanish Lymphoma/Autologous Bone Marrow Transplant Study Group (GELTAMO), Salamanca, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Alcoceba
authors.affiliation: Hematopathology Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Martín-García
authors.affiliation: Department of Pathology, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Blanco
authors.affiliation: Department of Statistics, University of Salamanca, Salamanca, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Sanchez-Barba
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Balanzategui
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Marín
authors.affiliation: Spanish Lymphoma/Autologous Bone Marrow Transplant Study Group (GELTAMO), Salamanca, Spain.|Department of Pathology, University Hospital of Marqués de Valdecilla/IFIMAV, Santander, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Montes-Moreno
authors.affiliation: Spanish Lymphoma/Autologous Bone Marrow Transplant Study Group (GELTAMO), Salamanca, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: González-Barca
authors.affiliation: Spanish Lymphoma/Autologous Bone Marrow Transplant Study Group (GELTAMO), Salamanca, Spain.
authors.forename: Emilia
authors.initials: E
authors.lastname: Pardal
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Jiménez
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: García-Álvarez
authors.affiliation: Hematopathology Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Guillem
authors.initials: G
authors.lastname: Clot
authors.affiliation: Fundación Pública Galega de Medicina Xenómica, IDIS, SERGAS, Santiago de Compostela, Spain.|Grupo de Medicina Xenómica, CIBERER, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Carracedo
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
authors.forename: Norma C
authors.initials: NC
authors.lastname: Gutiérrez
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Sarasquete
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Chillón
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Corral
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Prieto-Conde
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.|Spanish Lymphoma/Autologous Bone Marrow Transplant Study Group (GELTAMO), Salamanca, Spain.
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Caballero
authors.affiliation: Hematopathology Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Salaverria
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain. rgarcias@usal.es.|Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain. rgarcias@usal.es.|Spanish Lymphoma/Autologous Bone Marrow Transplant Study Group (GELTAMO), Salamanca, Spain. rgarcias@usal.es.|Center for Cancer Research (CIC, IBMCC-USAL-CSIC), Salamanca, Spain. rgarcias@usal.es.
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.affiliation: Molecular Biology & Histocompatibility Unit, Department of Hematology, IBSAL - University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.|Center for Cancer Research (CIC, IBMCC-USAL-CSIC), Salamanca, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: González
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods
keywords: CNA; CNN-LOH; Diffuse large B cell lymphoma; GC; Non-GC; Paired samples