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Prognostic analysis of aberrant somatic hypermutation of RhoH gene in diffuse large B cell lymphoma

Leukemia volume 21, pages 1846–1847 (2007)Cite this article

Previous reports demonstrated the aberrant somatic hypermutation (SHM) of proto-oncogenes PIM-1, MYC, RhoH and PAX5 as a novel mechanism of genetic lesion in diffuse large B-cell lymphoma (DLBCL).1 The Rho family of small GTPases including Rho, Rac, and Cdc42 has been well characterized as molecular switches to transduce signals from plasma membrane to the downstream effectors. RhoH, a member of the Rho family, is specifically expressed in hematopoietic cells, especially in T and B lymphocytes, and has been reported to downregulate Rac2 and LFA-1.3 As RhoH is GTPase-deficient and constitutively active, GTP-bound form,4 the activity of RhoH is directly related to the level of expression. Aberrant SHM of RhoH gene are distributed in intron 1 (+300∼1700) and have been reported in 46% of DLBCL,1 11% of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL),5 11% of primary cutaneous follicular center lymphoma (PCFCL),6 31% of primary cutaneous large B cell lymphoma, leg type (PCLBCL),6 and 13% of hepatitis C virus (HCV) associated non Hodgkin lymphoma.7 Although several studies reported the SHM of DLBCL and other lymphoid malignancy, the prognostic values of SHM remain elusive. Here, we have screened for SHM of RhoH gene in the lymph node samples from 100 previously untreated DLBCL cases.

These patients were diagnosed and treated at Nagoya University Hospital since 1987 to 2002, and median duration of follow-up was 1026 days. Informed consent was obtained from all patients. Samples from 12 cases of reactive lymphadenopathy were also screened for negative control. Intron 1 of RhoH gene was amplified and screened by the denaturing HPLC (DHPLC) analysis using the WAVE Maker System (Transgenomic Inc., San Jose, CA, USA) as previously described.8 DHPLC gradients and temperatures were determined using WAVE Maker System software. When heterozygous profiles were identified by visual inspection of the chromatograms, amplified products were cloned into pGEM-T easy vector (Promega, Madison, WI, USA) and were sequenced on the DNA sequencer (310; Applied Biosystems, Foster City, CA, USA) using the BigDye terminator cycle-sequencing kit (Applied Biosystems). Statistical analyses were performed using the Fisher exact test for 2 × 2 tables with StatView-J 5.5 software (Abacus Concepts Inc., Berkeley, CA, USA).

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Acknowledgements

This work was supported by Grants-in-Aid from the Sankyo Foundation of Life Science, National Institute of Biomedical Innovation and the Scientific Research of the Ministry of Education, Culture, Sports, Science and Technology, Japan. We thank Ms Satomi Yamaji and Chika Wakamatsu for their excellent technical help.

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  1. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan

    J Hiraga, A Katsumi, T Iwasaki, A Abe, T Matsushita, T Kinoshita & T Naoe

  2. Department of Infectious Diseases, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan

    H Kiyoi

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  1. J Hiraga
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Correspondence to A Katsumi.

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Hiraga, J., Katsumi, A., Iwasaki, T. et al. Prognostic analysis of aberrant somatic hypermutation of RhoH gene in diffuse large B cell lymphoma. Leukemia 21, 1846–1847 (2007). https://doi.org/10.1038/sj.leu.2404717

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