t(11;14) in Mantle Cell Lymphoma
The t(11;14)(q13;q32) chromosomal translocation is the pathognomonic genetic hallmark of mantle cell lymphoma (MCL), present in up to 70-100% of cases, and results in juxtaposition of the CCND1 gene (also known as BCL-1) at 11q13 with the immunoglobulin heavy chain (IGH) gene at 14q32, leading to constitutive overexpression of cyclin D1 protein. 1, 2, 3
Molecular Mechanism
- The translocation fuses the CCND1 gene on chromosome 11 with the IGH enhancer region on chromosome 14, causing deregulation of the cell cycle regulatory protein cyclin D1 2, 4
- Breakpoints on chromosome 14 occur 5' to one of six JH segments, while breakpoints on chromosome 11 are scattered: only 30-50% occur within a 1 kb major translocation cluster (MTC), with the remainder distributed over approximately 120 kb 3, 4
- This widespread distribution of breakpoints makes molecular detection by PCR feasible only for MTC-positive cases 3
Diagnostic Significance
- t(11;14) is detected in approximately 70-75% of MCL cases by conventional cytogenetics, but interphase FISH reveals the translocation in virtually all cases (approaching 100%), indicating that standard karyotyping underestimates its true frequency 1, 5
- The translocation is considered a critical primary event in MCL pathogenesis and serves as an essential diagnostic marker, particularly when histopathologic differentiation from other low-grade B-cell lymphomas is difficult 4, 5
- Detection is clinically important given MCL's poor prognosis compared to other low-grade non-Hodgkin's lymphomas 4
Detection Methods
- Interphase fluorescence in situ hybridization (FISH) using dual-color probes targeting IGH and CCND1 is the gold standard diagnostic method, as it overcomes limitations of conventional cytogenetics (low metaphase yield) and PCR (scattered breakpoints) 1, 2, 4
- FISH demonstrates colocalization of IGH and BCL-1 signals in translocation-positive cells, with samples showing >10% positive cells considered diagnostic for clonal t(11;14) 4
- TaqMan-based real-time PCR can detect and quantify IGH/BCL1 fusion products in MTC-positive cases for monitoring minimal residual disease 3
Clinical Context: Distinguishing from Multiple Myeloma
While the provided evidence focuses heavily on t(11;14) in multiple myeloma (MM), it's critical to note that t(11;14) has fundamentally different clinical implications in MCL versus MM:
- In MM, t(11;14) occurs in approximately 15% of cases and is associated with CD20 expression, lymphoplasmacytic morphology, and generally neutral to favorable prognosis 6
- In primary plasma cell leukemia (PCL), t(11;14) is paradoxically more frequent (71% in some series) but associated with aggressive disease when combined with high-risk features like p53 loss 6
- The key distinction is that t(11;14) defines MCL as a diagnostic entity, whereas in MM it represents one of several prognostic subgroups 6