Transformed diffuse large B-cell lymphomas with gains of the discontinuous 12q12-14 amplicon display concurrent deregulation of CDK2, CDK4 and GADD153 genes.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72579
Title:
Transformed diffuse large B-cell lymphomas with gains of the discontinuous 12q12-14 amplicon display concurrent deregulation of CDK2, CDK4 and GADD153 genes.
Authors:
Al-Assar, Osama; Rees-Unwin, Karen S; Menasce, Lia P; Hough, Rachael E; Goepel, John R; Hammond, David W; Hancock, Barry W
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.
Affiliation:
Yorkshire Cancer Research Institute for Cancer Studies, Division of Genomic Medicine, University of Sheffield, Sheffield, UK. o.al.assar@sheffield.ac.uk
Citation:
Transformed diffuse large B-cell lymphomas with gains of the discontinuous 12q12-14 amplicon display concurrent deregulation of CDK2, CDK4 and GADD153 genes. 2006, 133 (6):612-21 Br. J. Haematol.
Journal:
British Journal of Haematology
Issue Date:
Jun-2006
URI:
http://hdl.handle.net/10541/72579
DOI:
10.1111/j.1365-2141.2006.06093.x
PubMed ID:
16704435
Type:
Article
Language:
en
ISSN:
0007-1048
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorAl-Assar, Osama-
dc.contributor.authorRees-Unwin, Karen S-
dc.contributor.authorMenasce, Lia P-
dc.contributor.authorHough, Rachael E-
dc.contributor.authorGoepel, John R-
dc.contributor.authorHammond, David W-
dc.contributor.authorHancock, Barry W-
dc.date.accessioned2009-07-06T11:49:58Z-
dc.date.available2009-07-06T11:49:58Z-
dc.date.issued2006-06-
dc.identifier.citationTransformed diffuse large B-cell lymphomas with gains of the discontinuous 12q12-14 amplicon display concurrent deregulation of CDK2, CDK4 and GADD153 genes. 2006, 133 (6):612-21 Br. J. Haematol.en
dc.identifier.issn0007-1048-
dc.identifier.pmid16704435-
dc.identifier.doi10.1111/j.1365-2141.2006.06093.x-
dc.identifier.urihttp://hdl.handle.net/10541/72579-
dc.description.abstractTransformation 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.en
dc.language.isoenen
dc.subjectCancer DNA-
dc.subjectCancer Proteins-
dc.subjectTumour Cells-
dc.subjectTumour Markers-
dc.subject.meshChromosomes, Human, Pair 12-
dc.subject.meshCyclin-Dependent Kinase 2-
dc.subject.meshCyclin-Dependent Kinase 4-
dc.subject.meshDNA, Neoplasm-
dc.subject.meshDisease Progression-
dc.subject.meshHumans-
dc.subject.meshLymphoma, B-Cell-
dc.subject.meshLymphoma, Follicular-
dc.subject.meshLymphoma, Large B-Cell, Diffuse-
dc.subject.meshNeoplasm Proteins-
dc.subject.meshPolymerase Chain Reaction-
dc.subject.meshTranscription Factor CHOP-
dc.subject.meshTumor Cells, Cultured-
dc.subject.meshTumor Markers, Biological-
dc.titleTransformed diffuse large B-cell lymphomas with gains of the discontinuous 12q12-14 amplicon display concurrent deregulation of CDK2, CDK4 and GADD153 genes.en
dc.typeArticleen
dc.contributor.departmentYorkshire Cancer Research Institute for Cancer Studies, Division of Genomic Medicine, University of Sheffield, Sheffield, UK. o.al.assar@sheffield.ac.uken
dc.identifier.journalBritish Journal of Haematologyen

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