Multiple chromosomal abnormalities have been found in extranodal marginal zone B-cell lymphomas (MZLs) (low-grade BCLs of mucosa-associated lymphoid tissue [MALTomas]), and recent reports suggest that low-grade MALTomas of different sites have different chromosomal abnormalities. Testing for these abnormalities is helpful in confirmation of primary diagnosis and prediction of prognosis. Diagnostic and prognostic testing for these chromosomal abnormalities usually is performed by multicolor FISH assays.
Trisomy 3 occurs in more than 50% of low-grade MALTomas. Comparative genomic hybridization studies have shown gains at 3q21-23 and 3q25-29, suggesting that BCL6 is involved in some cases.
Trisomy 18 occurs in approximatey 30% of low-grade MALTomas. The genes involved are not well understood and the clinical relevance is unknown.
The most common translocation in gastric, intestinal, and lung MALTomas is t(11;18)(q21;q21) and occurs in 30% to 50% of cases.10-14 It is associated with a worse prognosis, and is seen most frequently in H. pylori-positive, antibiotic-resistant, or advanced gastric MZL. It is not seen in nodal or splenic MZL, or in extranodal MZL with increased large cells or large-cell transformation. The genes involved are the apoptosis inhibitor gene (API2) on 11q21, a member of the IAP family with caspase-inhibitory functions, and the MALT1 gene on 18q21, encoding a human paracaspase protein. The API2/MALT1 translocation results in a chimeric transcript and a fusion protein, which leads to inhibition of apoptosis and confers a survival advantage on the MZL cells. FISH is the most sensitive and specific method for detection of this translocation; however, RT-PCR also is used for detection.
An apoptosis regulatory molecule, BCL10, is overexpressed as a result of the t(1;14)(p22;q32) translocation, which involves BCL10 on 1p22 and the IGH gene on 14q32.15 Advanced MALTomas sometimes have both API2/MALT1 and BCL10/IGH translocations, and BCL10 appears to interact with API2/MALT1 fusion products to synergize activation of NF-kB, suggesting that they are part of a common pathway. Not many molecular laboratories offer testing for this translocation, because abnormal (nuclear) BCL10 protein expression can be used as a surrogate assay for this translocation. Nuclear BCL10 protein expression also may be seen in MZL with the t(11;18) translocation. The BCL10/IGH translocation is associated with a worse prognosis in low-grade MALTomas.
Recently described, the t(14;18)(q32;q21) translocation, detected by FISH, involves IGH on 14q32 and MALT1 on 18q21.16 It has been found in most liver MALTomas, as well as some cutaneous, ocular adnexal, and salivary gland lesions, but is rare in MALTomas of the stomach, intestine, lung, thyroid, and breast. It does not occur in nodal or splenic MZL. In a series of extranodal MALTomas, the IGH/MALT1 translocation was not found to coexist with the API2/MALT1 translocation but was sometimes found with trisomy 3 or trisomy 18 or both. The clinical significance of this translocation is not yet established. This translocation should not be confused with the cytogeneti-cally identical, but molecularly distinct, t(14;18)(q32;q21)-IGH/BCL2 translocation associated with follicular lymphoma.
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