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Genome-wide array-based CGH for mantle cell lymphoma: identification of homozygous deletions of the proapoptotic gene BIM

Oncogene volume 24, pages 1348–1358 (2005)Cite this article

Abstract

Mantle cell lymphoma (MCL) is characterized by 11q13 chromosomal translocation and CCND1 overexpression, but additional genomic changes are also important for lymphomagenesis. To identify the genomic aberrations of MCL at higher resolutions, we analysed 29 patient samples and seven cell lines using array-based comparative genomic hybridization (array CGH) consisting of 2348 artificial chromosome clones, which cover the whole genome at a 1.3 mega base resolution. The incidence of identified genomic aberrations was generally higher than that determined with chromosomal CGH. The most frequent imbalances detected by array CGH were gains of chromosomes 3q26 (48%), 7p21 (34%), 6p25 (24%), 8q24 (24%), 10p12 (21%) and 17q23 (17%), and losses of chromosomes 2p11 (83%), 11q22 (59%), 13q21 (55%), 1p21–p22 (52%), 13q34 (52%), 9q22 (45%), 17p13 (45%), 9p21 (41%), 9p24 (41%), 6q23–q24 (38%), 1p36 (31%), 8p23 (34%), 10p14 (31%), 19p13 (28%), 5q21 (21%), 22q12 (21%), 1q42 (17%) and 2q13 (17%). Our analyses also detected several novel recurrent regions of loss located at 1p36, 1q42.2–q43, 2p11.2, 2q13, 17p13.3 and 19p13.2–p13.3, as well as recurrent regions of homozygous loss such as 2p11 (Igκ), 2q13 and 9p21.3–p24.1 (INK4a/ARF). Of the latter, we investigated the 2q13 loss, which led to identification of homozygous deletions of the proapoptotic gene BIM. The high-resolution array CGH technology allowed for the precise identification of genomic aberrations and identification of BIM as a novel candidate tumor suppressor gene in MCL.

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Acknowledgements

The outstanding technical assistance of Ms H Suzuki and Y Kasugai is very much appreciated. We also wish to thank Dr Ryuzo Ohno, the chancellor of Aichi Cancer Center, for his general support. This work was supported in part by a Grant-in-Aid from the Ministry of Health, Labour and Welfare, a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, a Grant-in-Aid (B2) from the Japan Society for the Promotion of Science, a Grant-in-Aid from the Foundation of Promotion of Cancer Research, a Grant-in-Aid for Cancer Research from the Princess Takamatsu Cancer Research Fund and a Grant-in-Aid from the China Japan Medical Association.

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Authors and Affiliations

  1. Division of Molecular Medicine, Aichi Cancer Center Research Institute, 1-1-1 Kanokoden, Chikusa-ku, Aichi, Nagoya, 464-8681, Japan

    Hiroyuki Tagawa, Sivasundaram Karnan, Ritsuro Suzuki, Xiaohua Zhang, Akinobu Ota & Masao Seto

  2. Division of Epidemiology, Aichi Cancer Center Research Institute, 1-1-1 Kanokoden, Chikusa-ku, Aichi, Nagoya, 464-8681, Japan

    Keitaro Matsuo

  3. Department of Hematology and Chemotherapy, Aichi Cancer Center Hospital, Aichi, 464-8681, Japan

    Yasuo Morishima

  4. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Aichi, 464-8681, Japan

    Shigeo Nakamura

  5. Department of Pathology, Yan'an University School of Medicine, Yan'an, 716000, PR China

    Xiaohua Zhang

  6. Immuno-Biological Laboratories Co., Ltd, Gunma, 375-0005, Japan

    Akinobu Ota

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  1. Hiroyuki Tagawa
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Correspondence to Masao Seto.

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Tagawa, H., Karnan, S., Suzuki, R. et al. Genome-wide array-based CGH for mantle cell lymphoma: identification of homozygous deletions of the proapoptotic gene BIM. Oncogene 24, 1348–1358 (2005). https://doi.org/10.1038/sj.onc.1208300

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