Identification of Subtype-Specific Genomic Alterations of Acute and Lymphoma Types of Adult T-Cell Leukemia/Lymphoma.

Blood - Tập 106 - Trang 4667 - 2005
Aya Oshiro1, Hiroyuki Tagawa1, Kouichi Oshima2, Kennosuke Karube2, Naokuni Uike3, Yukie Tashiro4, Atae Utsunomiya5, Masato Masuda6, Yasuo Morishima7, Shigeo Nakamura8, Masao Seto1
1Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan
2Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
3Department of Hematology, National Kyushu Cancer Center, Fukuoka, Japan
4Department of Pathology, Imakiire General Hospital, Kagoshima, Japan
5Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Japan;
6Second Department of Internal Medicine, University Hospital, University of the Ryukyus, Nishihara, Okinawa, Japan
7Division of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
8Division of Molecular Diagnosis, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan

Tóm tắt

Abstract Background: Adult T cell leukemia/lymphoma (ATLL) is a human T-lymphotropic virus type-I mediated neoplasm and four major clinical subtypes are recognized; i.e., smoldering, chronic, lymphoma and acute types. Among these subtypes, acute and lymphoma types are fetal disease with poor prognosis. Although these two subtypes represent different clinical features, detailed analysis for genomic/genetic differences has not been sufficiently investigated. Purpose: To investigate genomic aberrations of these subtypes, we performed array-based comparative genomic hybridization (array CGH: 2308 BAC clones spotted in duplicate) for 66 cases of ATLL (17 cases of acute and 49 cases of lymphoma subtypes). To determine target genes in recurrently amplified regions, quantitative real-time PCR (RQ-PCR) was conducted. Results: Array CGH: Comparison of genome profiles revealed that lymphoma type shows more frequent gain and loss than those of acute type. The numbers of respective genomic gain and loss regions of lymphoma type were 9.7 and 9.8 on average. The numbers of genomic gain and loss regions of acute type were 4.2 and 4.5 on average. Gain of 1q, 2p, 4q, 7p and 7q, and loss of 10p, 13q, 16q and 18p were characteristic to lymphoma type whereas gain of 3p and 3q was specific to acute type. Recurrent high-level amplifications were found at 1p35, 6p25, 7p22.2, 7q21–q22, 7q31–q36 and 14q32 in lymphoma type. However, such genomic amplifications were not found in acute type. RQ-PCR: CARMA1 (7p22 locus), which encodes signaling proteins associated with development of B and T cells, was a possible target of the 7p22 amplification in lymphoma type. The extremely higher expression of BCL11B (14q32 locus) which is a key regulator of both differentiation and survival during thymocyte development, was found in acute type irrespective of the 14q32 amplification. However, no overexpression of BCL11B was found in lymphoma type with high copy number gain, indicating that BCL11B is not the target gene for 14q32 amplification in the lymphoma type. Conclusion: Array-CGH revealed that patterns of genomic aberrations between acute and lymphoma types were different. Quantitative gene expression analysis also implicated distinct mechanism of aberrant gene expressions between acute and lymphoma types. Combination of array-CGH and quantitative gene expression analysis provided evidence that the acute and lymphoma types are developed via distinct genomic/genetic pathways.

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Blood

Tập 106

4667

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