Ongoing monoclonal B-cell proliferation is not common in gastric B-cell lymphoma after combined radiochemotherapy.

PURPOSE: Gastric marginal-zone B-cell lymphoma (MZBCL) of the mucosa-associated lymphoid tissue (MALT) is associated with chronic Helicobacter pylori gastritis. Stable complete remission (CR) can be induced by H pylori eradication. Whether this is paralleled by cure of the lymphoma remains unclear. Persisting monoclonal bands for immunoglobulin heavy chain variable region (VH) representing the lymphoma clone have been described in up to 50% of patients in CR. This retrospective study investigated whether this phenomenon also occurs after radiochemotherapy. PATIENTS AND METHODS: Biopsy samples of 20 patients receiving chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone and irradiation were analyzed before and after therapy. Study patients had Ann Arbor stage I/II primary gastric cancer, including four cases of MZBCL of MALT type, 12 cases of diffuse large-cell lymphomas (DLCL), and four cases of mixed MALT type/DLCL. Polymerase chain reaction (PCR) for VH rearrangement was performed. Monoclonal PCR products were cloned and sequenced. RESULTS: Fourteen of 20 patients had a monoclonal or oligoclonal band distribution at diagnosis converted into polyclonal pattern after radiochemotherapy. Of the remaining six patients, two were lost to follow-up. One patient did not respond and died of progressive disease. PCR in this patient showed persistent B-cell clonality. In three patients, the initial PCR showed a polyclonal pattern and thus could not be evaluated during follow-up. CONCLUSION: In contrast with H pylori eradication alone, radiochemotherapy results in clearing of monoclonal cells during follow-up. This may result in better elimination of residual lymphoma cells. Further study is needed to determine whether this translates into lower risk of relapse.

Identification and characterization of mouse SSX genes: a multigene family on the X chromosome with restricted cancer/testis expression.

Human SSX was first identified as the gene involved in the t(X;18) translocation in synovial sarcoma. SSX is a multigene family, with 9 complete genes on chromosome Xp11. Normally expressed almost exclusively in testis, SSX mRNA is expressed in various human tumors, defining SSX as a cancer/testis antigen. We have now cloned the mouse ortholog of SSX. Mouse SSX genes can be divided into Ssxa and Ssxb subfamilies based on sequence homology. Ssxa has only one member, whereas 12 Ssxb genes, Ssxb1 to Ssxb12, were identified by cDNA cloning from mouse testis and mouse tumors. Both Ssxa and Ssxb are located on chromosome X and show tissue-restricted mRNA expression to testis among normal tissues. All putative human and mouse SSX proteins share conserved KRAB and SSX-RD domains. Mouse tumors were found to express some, but not all, Ssxb genes, similar to the SSX activation in human tumors.

A new member of the NY-ESO-1 gene family is ubiquitously expressed in somatic tissues and evolutionarily conserved.

The NY-ESO-1 gene, located on chromosome Xq28, encodes a cancer/testis antigen in human. Normally expressed only in germ cells, NY-ESO-1 is activated in a wide range of human tumors, eliciting both antibody and cell-mediated immune responses in cancer patients. Clinical immunotherapeutic trials NY-ESO-1 gene products are now ongoing. A closely related gene, LAGE-1, was subsequently identified and shares similar biological features. By database search, we have identified a third member of the human NY-ESO-1 gene family. This gene, designated ESO3, is also located on the X chromosome, clustered with two exact copies of ESO1(NY-ESO-1) and one copy of ESO2(LAGE-1), within a approximately 400 kb segment. The exon-intron structures are conserved among ESO1-3. While ESO1 and ESO2(LAGE-1) share >80% protein sequence identity, homology between ESO3 and the other two members is lower (<50%). ESO3 is also distinctive in that, unlike ESO1 and 2 that are normally expressed only in testis, ESO3 messenger RNA (mRNA) is ubiquitously expressed in somatic tissues. In addition to ESO3, an intronless pseudogene highly homologous to ESO3 was found on chromosome 9, designated psiESO3.A search of the rodent databases identified mouse and rat counterparts of ESO3, named mESO3 and rESO3. mESO3 is similarly located on mouse X chromosome, with conserved exon-intron junctions. Protein sequence of mESO3 is 54% identical to ESO3 (70% identical at the conserved carboxyl end), and 32% to ESO1. mESO3 mRNA is also ubiquitously expressed in somatic tissues, as is rESO3. In addition, an intronless and presumably non-coding, copy of the mESO3, psimESO3, was identified on mouse chromosome 15. No counterpart of the ESO1 or 2 genes was found in rodents.