title: Transformed diffuse large B-cell lymphomas with gains of the discontinuous 12q12-14 amplicon display concurrent deregulation of CDK2, CDK4 and GADD153 genes.
abstract: Transformation of the indolent follicular lymphoma (FL) to the aggressive diffuse large B-cell lymphoma (DLBCL) results in resistance to therapy with shortened survival. It has been demonstrated that the 12q12-14 region was mainly amplified in DLBCL cases but not in their FL counterparts. Therefore, we examined the DNA copy number and protein expression profiles for CDK2, CDK4 and GADD153, three genes that map to 12q12-14, in a set of 44 paired FL/DLBCL samples from 22 patients. The concordant amplification of these genes occurred in seven of 22 (32%) of FL cases, compared with 15 of 22 (68%) of DLBCL cases. At the protein level, 15 of 22 of the DLBCL samples (68%) showed strong staining for the CDK2 protein, compared with five of 21 of FL samples (24%). The majority of the DLBCL samples (16/22, 72%) expressed the CDK4 protein, whereas the majority of the FL samples (12/21, 57%) showed no expression of this protein. Except for one DLBCL case, no expression of the GADD153 protein could be detected. The deregulation of the CDK2 and CDK4 genes at the genetic and protein levels suggest a functional role for these genes in the transformation process and could potentially provide targets for prognostic tests or therapeutic interventions.
authors.affiliation: Yorkshire Cancer Research Institute for Cancer Studies, Division of Genomic Medicine, University of Sheffield, Sheffield, UK. o.al.assar@sheffield.ac.uk
authors.forename: Osama
authors.initials: O
authors.lastname: Al-Assar
authors.forename: Karen S
authors.initials: KS
authors.lastname: Rees-Unwin
authors.forename: Lia P
authors.initials: LP
authors.lastname: Menasce
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Hough
authors.forename: John R
authors.initials: JR
authors.lastname: Goepel
authors.forename: David W
authors.initials: DW
authors.lastname: Hammond
authors.forename: Barry W
authors.initials: BW
authors.lastname: Hancock
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism; D008224:Lymphoma, Follicular / Q000235:genetics / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C497249:DDIT3 protein, human; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D051742:Transcription Factor CHOP; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4