The t(11;18) (q21;q21) translocation is a characteristic chromosomal aberration in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. We previously identi®ed a YAC clone y789F3, which includes the breakpoint at 18q21 in a MALT lymphoma patient. BAC and PAC contigs were constructed on the YAC, and BAC 193f9 was found to encompass the breakpoint region. In the present study, we further narrowed down the breakpoint region at 18q21 in ®ve MALT lymphoma patients by means of FISH and Southern blot analyses using the plasmid contig constructed from BAC 193f9. The breakpoints at 18q21 in three of the ®ve MALT lymphoma patients were found to be clustered approximately within the 20 kb region. By using exon ampli®cation and cDNA library screening, we identi®ed a novel cDNA spanning the breakpoint region that exhibited aberrant mRNA signals in four of the ®ve MALT lymphoma patients. The nucleotide sequence predicted an 813 amino acid protein that shows signi®cant sequence similarity to the CD22b and laminin 5 a3b subunit. We refer to the gene encoding this transcript as MALT1 (Mucosa-Associated Lymphoid Tissue lymphoma translocation gene 1). The alteration of MALT1 by translocation strongly suggests that this gene plays an important role in the pathogenesis of MALT lymphoma.

Recent progress in molecular analysis of low-grade B cell lymphoma has revealed that API2 at 11q21 and a novel gene, MALT1 at 18q21, are involved in t(11;18)(q21;q21), a characteristic chromosome aberration for mucosa-associated lymphoid tissue (MALT) type lymphoma. We describe here the establishment of a reverse transcription-polymerase chain reaction (RT-PCR) assay that we used to analyze 22 cases of MALT lymphoma. All five cases that were shown to possess t(11;18)(q21;q21) showed the specific amplification of API2-MALT1 chimeric transcripts. Of the remaining 17 cases for which cytogenetic data were not available, three cases demonstrated the presence of fusion transcripts, indicating that a significant percentage of MALT lymphoma cases of the present series appeared to possess t(11;18). A single fragment was observed in each of these cases, but the size varied from case to case. Sequencing analysis revealed that there are two breakpoints in API2 and three in MALT1, and that all of the fusion transcripts are in-frame. On the basis of these results, four kinds of chimeric proteins can be predicted for the present series. Thus, the RT-PCR assay used here should serve as an effective molecular tool for understanding molecular pathogenesis and the clinical significance of API2-MALT1 for MALT lymphomas.

We found four novel mutations in the NCCT gene in seven Japanese patients with GS. Moreover, our study suggests that the distribution of mutations in the NCCT gene in Japanese GS patients potentially differs from that in other populations.

No abstract

Angioimmunoblastic T-cell lymphoma (AITL) is a distinct peripheral T-cell lymphoma entity exhibiting peculiar clinical features and poor prognosis. Its clinical characteristics and prognostic factors are not well established. To clarify the clinical characteristics and prognostic features of AITL, we conducted a multicenter, retrospective study. Fifty-six patients were enrolled. The median patient age was 68 years. Immunohistochemical examinations of tumor cells showed positivity for CD10 and T-cell markers, and chromosomal examination detected several types of abnormalities. More than 80 % of patients show advanced disease at diagnosis and poor prognostic scores. A high proportion of patients showed accompanying B symptoms, splenomegaly, and hepatomegaly at diagnosis. The 5-year overall survival (OS) rate was 48 % and progression-free survival was 25 %. Univariate analysis revealed higher age, fever, poor performance status, anemia, and low albumin level to be poor prognostic factors for OS. In addition to these factors, both IPI and PIT were also predictive of OS. Multivariate analysis indicated only a low level of serum albumin to be a significant prognostic factor for OS. Serum albumin may be one of the important prognostic factors for AITL. Further investigation is needed to confirm these results.