Detection of somatic quantitative genetic alterations by multiplex polymerase chain reaction for the prediction of outcome in diffuse large B-cell lymphomas
| Autor: | G Buchonnet, Christian Bastard, Mario Tosi, Hervé Tilly, Françoise Parmentier, Fabrice Jardin, Sabine Quief, Jean-Pierre Kerckaert, Philippe Ruminy, Jean-Michel Picquenot, Céline Villenet, Thierry Frebourg |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Adolescent Gene Dosage Biology Polymerase Chain Reaction Gene dosage law.invention Antibodies Monoclonal Murine-Derived Nucleic acid thermodynamics law hemic and lymphatic diseases Antineoplastic Combined Chemotherapy Protocols Proto-Oncogenes Gene duplication Multiplex polymerase chain reaction medicine Humans Genes Tumor Suppressor neoplasms Polymerase chain reaction Aged Aged 80 and over Chromosome Aberrations Gene Amplification Hematopoietic Stem Cell Transplantation Antibodies Monoclonal Nucleic Acid Hybridization Hematology Middle Aged Prognosis medicine.disease BCL6 Combined Modality Therapy Molecular biology Neoplasm Proteins Treatment Outcome Female Lymphoma Large B-Cell Diffuse Rituximab Diffuse large B-cell lymphoma Gene Deletion Comparative genomic hybridization |
| Zdroj: | Haematologica. 93:543-550 |
| ISSN: | 1592-8721 0390-6078 |
| Popis: | Background Genomic gains and losses play a crucial role in the development of diffuse large B-cell lymphomas. High resolution array comparative genomic hybridization provides a comprehensive view of these genomic imbalances but is not routinely applicable. We developed a polymerase chain reaction assay to provide information regarding gains or losses of relevant genes and prognosis in diffuse large B-cell lymphomas.Design and Methods Two polymerase chain reaction assays (multiplex polymerase chain reaction of short fluorescent fragments, QMPSF) were designed to detect gains or losses of c-REL, BCL6, SIM1, PTPRK, MYC, CDKN2A, MDM2, CDKN1B, TP53 and BCL2. Array comparative genomic hybridization was simultaneously performed to evaluate the sensitivity and predictive value of the QMPSF assay. The biological and clinical relevance of this assay were assessed.Results The predictive value of the QMPSF assay for detecting abnormal DNA copy numbers ranged between 88–97%, giving an overall concordance rate of 92% with comparative genomic hybridization results. In 77 cases of diffuse large B-cell lymphomas, gains of MYC, CDKN1B, c-REL and BCL2 were detected in 12%, 40%, 27% and 29%, respectively. TP53 and CDKN2A deletions were observed in 22% and 36% respectively. BCL2 and CDKN2A allelic status correlated with protein expression. TP53 mutations were associated with allelic deletions in 45% of cases. The prognostic value of a single QMPSF assay including TP53, MYC, CDKN2A, SIM1 and CDKN1B was predictive of the outcome independently of the germinal center B-cell like/non-germinal center B-cell like subtype or the International Prognostic Index.Conclusions QMPSF is a reliable and flexible method for detecting somatic quantitative genetic alterations in diffuse large B-cell lymphomas and could be integrated in future prognostic predictive models. |
| Databáze: | OpenAIRE |
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