2000年2月
Molecular and clinical features of non-Burkitt's, diffuse large-cell lymphoma of B-cell type associated with the c-MYC/immunoglobulin heavy-chain fusion gene
JOURNAL OF CLINICAL ONCOLOGY
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- 巻
- 18
- 号
- 3
- 開始ページ
- 510
- 終了ページ
- 518
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- 出版者・発行元
- W B SAUNDERS CO
Purpose: t(8;14)(q24;q32) and/or c-MYC/immunoglobulin heavy-chain (IGH) fusion gene have been observed not only in Burkitt's lymphoma (BL) but also in a proportion of non-BL, diffuse large-cell lymphoma of B-cell type (DLCL), We explored molecular features of DLCL with c-MYC/IGH fusion and the impact of this genetic abnormality on clinical outcome of DLCL.
Patients and Methods: A total of 203 cases of non-BL DLCL were studied. Genomic DNA extracted from tumor tissues was subjected to long-distance polymerase chain reaction (LD-PCR) using oligonucleotide primers for exon 2 of c-MYC and for the four constant region genes of IGH.
Results: Twelve cases (5.9%) showed positive amplification; one had a c-MYC/C mu, nine had a c-MYC/C gamma, and two had a c-MYC/C alpha fusion sequence. Restriction and sequence analysis of the LD-PCR products, ranging from 2.3 to 9.4 kb in size, showed that breakage in the 12 cases occurred within a 1.5-kb region that included exon 1 of c-MYC in combination with breakpoints at the switch regions of IGH (10 of 12), In 10 cases, Myc protein encoded by the fusion genes demonstrated mutations and/or deletions. Six cases had additional molecular lesions in BCL-5 or BCL-6 and/or p53 genes. The age range of the 12 patients war 44 to 86 years, with a median age of 65.5 years. Five patients had stage I/II disease, and seven had stage III/IV disease. Lactate dehydrogenase was elevated in nine of 11 subjects. Seven showed involvement of the gastrointestinal tract, All patients were treated by surgery and/or chemoradiotherapy; six died of the disease within 1 year, resulting in the poorest 1- and 2-year survival rates among DLCL subgroups.
Conclusion: The c-MYC/IGH fusion gene of DLCL is identical to that of the sporadic type of BL (sBL), DLCL with c-MYC/IGH shares clinical features with sBL but is characterized further by an older age distribution. J Clin Oncol 18:510-518. (C) 2000 by American Society of Clinical Oncology.
Patients and Methods: A total of 203 cases of non-BL DLCL were studied. Genomic DNA extracted from tumor tissues was subjected to long-distance polymerase chain reaction (LD-PCR) using oligonucleotide primers for exon 2 of c-MYC and for the four constant region genes of IGH.
Results: Twelve cases (5.9%) showed positive amplification; one had a c-MYC/C mu, nine had a c-MYC/C gamma, and two had a c-MYC/C alpha fusion sequence. Restriction and sequence analysis of the LD-PCR products, ranging from 2.3 to 9.4 kb in size, showed that breakage in the 12 cases occurred within a 1.5-kb region that included exon 1 of c-MYC in combination with breakpoints at the switch regions of IGH (10 of 12), In 10 cases, Myc protein encoded by the fusion genes demonstrated mutations and/or deletions. Six cases had additional molecular lesions in BCL-5 or BCL-6 and/or p53 genes. The age range of the 12 patients war 44 to 86 years, with a median age of 65.5 years. Five patients had stage I/II disease, and seven had stage III/IV disease. Lactate dehydrogenase was elevated in nine of 11 subjects. Seven showed involvement of the gastrointestinal tract, All patients were treated by surgery and/or chemoradiotherapy; six died of the disease within 1 year, resulting in the poorest 1- and 2-year survival rates among DLCL subgroups.
Conclusion: The c-MYC/IGH fusion gene of DLCL is identical to that of the sporadic type of BL (sBL), DLCL with c-MYC/IGH shares clinical features with sBL but is characterized further by an older age distribution. J Clin Oncol 18:510-518. (C) 2000 by American Society of Clinical Oncology.
- リンク情報
- ID情報
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- ISSN : 0732-183X
- PubMed ID : 10653866
- Web of Science ID : WOS:000085192300008