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A Recurring Translocation, t(3;6)(q27;p21), in Non-Hodgkin's Lymphoma Results in Replacement of the 5' Regulatory Region of BCL6 with a Novel H4 Histone Gene¹

The First Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, 54 Shogoin-Kawaramachi, Sakyo-ku, Kyoto 606-01 [T. A., H. A., N. Y., H. O., M. O.]; The Third Department of Internal Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita 010 [I. M., N. T.]; and The First Department of Internal Medicine, Kansai Medical University, Moriguchi 570 [S. F.], Japan

3q27 translocations affecting the BCL6 gene can involve not only immunoglobulin genes (IG) but also other as yet uncharacterized chromosomal loci as partners. Here, we describe cloning of the junctional area of a recurring translocation, t(3;6)(q27;p21), in non-Hodgkin's lymphoma of B-cell type and isolation of clones from 6p21; high resolution fluorescence in situ hybridization mapped the clones to sub-band 6p21.3. Nucleotide sequence analysis of a fragment from the junctional area of 6p21 revealed the presence of a novel H4 histone gene that was included in the histone gene cluster on this particular region, and the same fragment detected 380-bp transcripts in hematological tumor cells. Breakpoints on 3q27 of two cases carrying t(3;6) were immediately 3' of the BCL6 exon 1, and the H4 histone gene was substituted for the 5' regulatory elements of BCL6. Because H4 gene expression is tightly coupled to DNA replication, this study suggested an immediate mechanism for deregulated expression of BCL6, leading to the development of non-Hodgkin's lymphoma.

¹ Supported by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare (7–30) and from the Ministry of Education, Science, Sports and Culture of Japan (07671196).

² To whom requests for reprints should be addressed. Phone: +81-75-751-4293; Fax: +81-75-751-3201; E-mail: ohnohito-kyt@umin.u.-tokyo.ac.jp.

Received 9/16/96. Accepted 11/18/96.

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