Array-Based Comparative Genomic Hybridization Analysis Reveals Recurrent Chromosomal Alterations and Prognostic Parameters in Primary Cutaneous Large B-Cell Lymphoma
| Autor: | Juliette J. Hoefnagel, Rein Willemze, Anton K. Raap, Ekaterina S. Jordanova, Remco Dijkman, Aat A. Mulder, Carla Rosenberg, Karoly Szuhai, Maarten H. Vermeer, Cornelis P. Tensen, Jeroen Knijnenburg |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Lymphoma B-Cell Skin Neoplasms Biology CDKN2A Gene duplication medicine Humans Promoter Regions Genetic B-cell lymphoma Aged Cyclin-Dependent Kinase Inhibitor p15 Oligonucleotide Array Sequence Analysis Aged 80 and over Chromosome Aberrations medicine.diagnostic_test Genes p16 Gene Amplification Large-cell lymphoma Nucleic Acid Hybridization DNA Methylation Middle Aged Prognosis medicine.disease Lymphoma Oncology DNA methylation Female Lymphoma Large B-Cell Diffuse Chromosome Deletion Comparative genomic hybridization Fluorescence in situ hybridization |
| Zdroj: | Journal of Clinical Oncology. 24:296-305 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2005.02.0842 |
| Popis: | Purpose To evaluate the clinical relevance of genomic aberrations in primary cutaneous large B-cell lymphoma (PCLBCL). Patients and Methods Skin biopsy samples of 31 patients with a PCLBCL classified as either primary cutaneous follicle center lymphoma (PCFCL; n = 19) or PCLBCL, leg type (n = 12), according to the WHO–European Organisation for Research and Treatment of Cancer (EORTC) classification, were investigated using array-based comparative genomic hybridization, fluorescence in situ hybridization (FISH), and examination of promoter hypermethylation. Results The most recurrent alterations in PCFCL were high-level DNA amplifications at 2p16.1 (63%) and deletion of chromosome 14q32.33 (68%). FISH analysis confirmed c-REL amplification in patients with gains at 2p16.1. In PCLBCL, leg type, most prominent aberrations were a high-level DNA amplification of 18q21.31-q21.33 (67%), including the BCL-2 and MALT1 genes as confirmed by FISH, and deletions of a small region within 9p21.3 containing the CDKN2A, CDKN2B, and NSG-x genes. Homozygous deletion of 9p21.3 was detected in five of 12 patients with PCLBCL, leg type, but in zero of 19 patients with PCFCL. Complete methylation of the promoter region of the CDKN2A gene was demonstrated in one PCLBCL, leg type, patient with hemizygous deletion, in one patient without deletion, but in zero of 19 patients with PCFCL. Seven of seven PCLBCL, leg type, patients with deletion of 9p21.3 and/or complete methylation of CDKN2A died as a result of their lymphoma. Conclusion Our results demonstrate prominent differences in chromosomal alterations between PCFCL and PCLBCL, leg type, that support their classification as separate entities within the WHO-EORTC scheme. Inactivation of CDKN2A by either deletion or methylation of its promoter could be an important prognostic parameter for the group of PCLBCL, leg type. |
| Databáze: | OpenAIRE |
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