Molecular testing may be performed initially to confirm the diagnosis of mantle cell lymphoma (MCL), as the diagnosis confers a very poor prognosis and mandates aggressive therapy.21 Diagnostic testing generally targets the t(11;14)(q13q32) translocation, which juxtaposes the BCLl/cyclin D1/PRAD1 gene on chromosome 11q13 with an IGH enhancer, resulting in overexpression of normal cyclin D1 protein and increased cell cycling. The translocation is not specific for MCL, as it also occurs in many multiple myelomas, but no diagnostic problems are caused by this overlap. Multiple methods have been used to detect the t(11;14), including karyotyping, Southern blot, PCR for t(11;14), RT-PCR for cyclin D1 messenger RNA (mRNA), and FISH.22 The optimal diagnostic method has proven to be FISH (illustration in Figure 32-2d), which detects >90% of cases, even in paraffin-embedded biopsy tissue. PCR detection is less successful because the 11q13 breakpoints are widely distributed; approximately 30% to 50% are localized to a 1kb DNA segment called the major translocation cluster (MTC), but the remaining translocations involve many different sites not easily detectable by PCR analysis. Quantitative RT-PCR assays on fresh or frozen tissue detect increased cyclin D1 mRNA in a high percent age of MCL,23 but there is little application for this cumbersome RT-PCR assay when FISH is faster, is more specific, and can be performed on paraffin-embedded tissue. ATM deletions like those in CLL/SLL also are seen in many MCL cases, and progression or aggressive clinical behavior in MCL is reported to be associated with P16 and TP53 abnormalities. MCLs rarely have somatic mutation of IgVH.
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