1. ¹Department of Radiation Biology, The Norwegian Radium Hospital, Oslo, Norway
2. ²Department of Immunology, The Norwegian Radium Hospital, Oslo, Norway
3. ³Department of Tumor Biology, The Norwegian Radium Hospital, Oslo, Norway
4. ⁴Department for Molecular Biosciences, University of Oslo, Oslo, Norway
5. ⁵Department of Pathology, The Norwegian Radium Hospital, Oslo, Norway
6. ⁶Cold Spring Harbor Laboratory, Genome Research Center, Woodbury, NY, USA
7. ⁷Institute of Pathology, Rikshospitalet, Oslo, Norway

Correspondence: Dr T Stokke, Department of Radiation Biology, The Norwegian Radium Hospital, Montebello, Oslo 0310, Norway. Fax: +47 22934270; E-mail: tstokke@radium.uio.no

Received 23 November 2004; Accepted 22 July 2005; Published online 29 September 2005.

Abstract

Gain of chromosome 18q and translocation t(14;18) are] frequently found in B-cell non-Hodgkin's lymphomas (B-NHL). Increased BCL2 transcription and BCL2 protein expression have been suggested to be the result of the gain. We utilized FISH, PCR and array CGH to study BCL2 and chromosome 18 copy number changes and rearrangements in 93 cases of B-NHL. BCL2 protein was expressed in >75% of the tumor cells in 92% of the cases by immunohistochemistry. Gain of BCL2 was associated with a 25% increase in BCL2 expression levels (immunoblotting), whereas t(14;18) resulted in a 55% increase in BCL2 levels compared to cases without BCL2 alterations. The tumor cell (spontaneous) apoptotic fractions were similar for the cases with different BCL2 genotypes. However, the normal cell apoptotic fractions were higher for the tumors with t(14;18) compared to the tumors without BCL2 alterations, while the tumors with gain of BCL2 only showed intermediate levels. Low-level gains of parts of chromosome 18 were found in 14 of the 38 B-NHL cases with t(14;18), with a consensus region 18pter-q21.33 that did not include the BCL2 gene. The 11 cases with 18q gain only showed a consensus region encompassing 18q21.2–18q21.32 and 18q21.33, which contain PMAIP1/MALT1 and BCL2, respectively.