Detection of BCL-6 rearrangements and p53 mutations in Malt-lymphomas.
Twenty-seven lymphomas of mucosa-associated lymphoid tissue (MALT) derived from distinct anatomical sites were tested for the presence of genetic lesions commonly involved in B-cell lymphomagenesis, including activation of proto-oncogenes (BCL-1, BCL-2, BCL-6, and c-MYC), disruption of tumor suppressor loci (p53, 6q), and infection by viruses [Epstein-Barr virus (EBV), and Kaposi's sarcoma-herpesvirus/human herpesvirus-8 (KSHV/HHV-8)]. Sixteen low-grade and 11 high-grade MALT-lymphomas were included in the study. The presence of genetic lesions was tested by a combination of molecular approaches, including Southern blot hybridization, polymerase chain reaction (PCR), and PCR-single strand conformation polymorphism followed by DNA direct sequencing. Alterations of BCL-1, BCL-2, or c-MYC, as well as infection by KSHV/HHV-8, scored negative in all MALT-lymphomas analysed. Conversely, rearrangements of BCL-6 and mutations of p53 clustered with a fraction of high-grade MALT-lymphomas. Deletions of 6q occurred in selected cases of both low- and high-grade MALT-lymphomas, whereas a monoclonal infection by EBV was restricted to one single patient. These data corroborate the notion that the molecular pathogenesis of MALT-lymphomas differs substantially from that of nodal B-cell lymphomas. Occasionally, however, a proportion of high-grade MALT-lymphomas may harbor selected genetic lesions among the ones commonly involved in nodal B-cell lymphomagenesis.
Gaidano
G
G
Dipartimento di Scienze Mediche, Università di Torino, Novara, Italy. gaidano@med.no.unipmn.it
Volpe
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G
Pastore
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C
Chiarle
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R
Capello
D
D
Gloghini
A
A
Perissinotto
E
E
Savinelli
F
F
Bosco
M
M
Mazza
U
U
Pileri
S
S
Palestro
G
G
Carbone
A
A
Saglio
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D015139:Blotting, Southern; D015342:DNA Probes / Q000737:chemistry; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D015321:Gene Rearrangement; D004854:Herpesvirus 4, Human / Q000235:genetics; D019288:Herpesvirus 8, Human / Q000235:genetics; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000473:pathology / Q000821:virology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D015342:DNA Probes; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53