T(11:14)

t(11;14)(q13;q32) is a chromosomal translocation that occurs in certain types of cancers, most notably in Mantle Cell Lymphoma (MCL) and multiple myeloma. This translocation involves the juxtaposition of the immunoglobulin heavy chain locus on chromosome 14 (IGH@) at band q32 to the cyclin D1 (CCND1) gene on chromosome 11 at band q13. The result of this translocation is the overexpression of the cyclin D1 protein, which promotes cell cycle progression and is a key event in the pathogenesis of these cancers.

Overview

The t(11;14)(q13;q32) translocation is considered a hallmark of Mantle Cell Lymphoma, a type of non-Hodgkin lymphoma characterized by the proliferation of B lymphocytes. It is also found in a subset of patients with multiple myeloma, a cancer of plasma cells. The presence of this translocation can influence the clinical behavior of the disease and has implications for diagnosis, prognosis, and treatment.

Pathophysiology

Cyclin D1, encoded by the CCND1 gene, is a regulatory protein involved in the transition from the G1 phase to the S phase of the cell cycle. In normal cells, the expression of cyclin D1 is tightly regulated. However, in cells harboring the t(11;14) translocation, the CCND1 gene is placed under the control of the IGH@ enhancer, leading to its overexpression. This dysregulation promotes unchecked cell division and contributes to the malignant phenotype of the affected cells.

Clinical Significance

The detection of the t(11;14)(q13;q32) translocation is of significant clinical importance. In Mantle Cell Lymphoma, it is used as a diagnostic marker and is associated with a more aggressive disease course compared to other lymphomas without this translocation. In multiple myeloma, the presence of t(11;14) is associated with specific clinical features and may influence the choice of therapeutic strategies.

Diagnosis

The diagnosis of t(11;14)(q13;q32) translocation is typically made using fluorescence in situ hybridization (FISH), a cytogenetic technique that allows for the visualization of specific DNA sequences on chromosomes. Polymerase chain reaction (PCR) and karyotyping can also be used to detect this translocation.

Treatment

The treatment of cancers associated with the t(11;14)(q13;q32) translocation is tailored to the specific type and stage of the disease. In Mantle Cell Lymphoma, treatment options may include chemotherapy, immunotherapy, and targeted therapies. In multiple myeloma, treatment usually involves a combination of chemotherapy, corticosteroids, and novel agents such as proteasome inhibitors and immunomodulatory drugs. The presence of the t(11;14) translocation can influence the choice of therapeutic agents.

Prognosis

The prognosis of patients with cancers harboring the t(11;14)(q13;q32) translocation varies depending on several factors, including the type of cancer, stage at diagnosis, and response to treatment. In general, Mantle Cell Lymphoma with this translocation is considered to have a poorer prognosis compared to other subtypes. In multiple myeloma, the prognostic significance of t(11;14) is more variable and may depend on the presence of additional cytogenetic abnormalities.

Conclusion

The t(11;14)(q13;q32) translocation is a critical genetic event in the pathogenesis of certain cancers, most notably Mantle Cell Lymphoma and multiple myeloma. Its detection plays a crucial role in the diagnosis, prognosis, and treatment of affected patients. Ongoing research into the molecular mechanisms underlying this translocation may provide new insights into targeted therapies for these diseases.