title: Cross-platform assessment of genomic imbalance confirms the clinical relevance of genomic complexity and reveals loci with potential pathogenic roles in diffuse large B-cell lymphoma.
abstract: Genomic copy number alterations (CNAs) in diffuse large B-cell lymphoma (DLBCL) have roles in disease pathogenesis, but overall clinical relevance remains unclear. Herein, an unbiased algorithm was uniformly applied across three genome profiling datasets comprising 392 newly-diagnosed DLBCL specimens that defined 32 overlapping CNAs, involving 36 minimal common regions (MCRs). Scoring criteria were established for 50 aberrations within the MCRs while considering peak gains/losses. Application of these criteria to independent datasets revealed novel candidate genes with coordinated expression, such as CNOT2, potentially with pathogenic roles. No one single aberration significantly associated with patient outcome across datasets, but genomic complexity, defined by imbalance in more than one MCR, significantly portended adverse outcome in two of three independent datasets. Thus, the standardized scoring of CNAs currently developed can be uniformly applied across platforms, affording robust validation of genomic imbalance and complexity in DLBCL and overall clinical utility as biomarkers of patient outcome.
authors: a Cancer Genetics, Inc. , Rutherford , NJ , USA ;
authors: Lizalynn M
authors: LM
authors: Dias
authors: a Cancer Genetics, Inc. , Rutherford , NJ , USA ;
authors: Venkata
authors: V
authors: Thodima
authors: a Cancer Genetics, Inc. , Rutherford , NJ , USA ;
authors: Julia
authors: J
authors: Friedman
authors: a Cancer Genetics, Inc. , Rutherford , NJ , USA ;
authors: Charles
authors: C
authors: Ma
authors: a Cancer Genetics, Inc. , Rutherford , NJ , USA ;
authors: Asha
authors: A
authors: Guttapalli
authors: a Cancer Genetics, Inc. , Rutherford , NJ , USA ;
authors: Geetu
authors: G
authors: Mendiratta
authors: b Hematopathology Section , University of Southern California Keck School of Medicine , CA , USA ;
authors: Imran N
authors: IN
authors: Siddiqi
authors: c Department of Pathology, Carver College of Medicine , University of Iowa , Iowa City , IA , USA ;
authors: Sergei
authors: S
authors: Syrbu
authors: d Cell Biology Program , Memorial Sloan-Kettering Cancer Center , New York , NY , USA ;|e Department of Medicine , Memorial Sloan-Kettering Cancer Center , New York , NY , USA.
authors: R S K
authors: RS
authors: Chaganti
authors: a Cancer Genetics, Inc. , Rutherford , NJ , USA ;
authors: Jane
authors: J
authors: Houldsworth
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D003520:Cyclophosphamide / Q000627:therapeutic use; D056915:DNA Copy Number Variations; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing; D014644:Genetic Variation; D023281:Genomics / Q000379:methods; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D040641:Quantitative Trait Loci; D000069283:Rituximab; D015398:Signal Transduction; D059467:Transcriptome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Lymphoma; molecular genetics; prognostication