Molecular Analysis of the T(14;18) Chromosomal Translocation in Malignant Lymphomas

TLDR

The t(14;18) translocation, which juxtaposes the bcl‑2 proto‑oncogene with the Ig heavy‑chain locus, is a frequent chromosomal abnormality in follicular lymphomas, but its prevalence in other lymphomas remains poorly defined due to cytogenetic challenges. The study aimed to assess the utility of chromosome‑18 DNA probes for detecting bcl‑2 abnormalities across Hodgkin’s and non‑Hodgkin’s lymphoma subtypes to improve diagnostic accuracy. Researchers applied multiple chromosome‑18 DNA probes to analyze various Hodgkin’s and non‑Hodgkin’s lymphoma subtypes for structural abnormalities near or within the bcl‑2 gene. The translocation was present in nearly all follicular neoplasms and about 28 % of diffuse large‑cell lymphomas, but absent in other Hodgkin’s and non‑Hodgkin’s subtypes, indicating a close pathogenetic link between bcl‑2 and a broad group of non‑Hodgkin’s lymphomas. N Engl J Med 1987; 317:1185–9.

Abstract

One of the most common karyotypic abnormalities is the t(14;18) translocation, which is found in many lymphomas that have a characteristic follicular morphology. Recent molecular studies have shown that this chromosomal translocation results in the juxtaposition of the candidate proto-oncogene bcl-2 (B-cell leukemia–lymphoma) on chromosome 18 with the immunoglobulin heavy-chain locus on chromosome 14. However, because performing accurate cytogenetic studies in solid hematolymphoid neoplasms is difficult, knowledge of the prevalence of the t(14;18) translocation and, by association, the extent of bcl-2 involvement in human lymphomas is limited. We used a number of chromosome-18 DNA probes to analyze various subtypes of Hodgkin's and non-Hodgkin's lymphomas and test for structural abnormalities near or within the bcl-2 gene. Molecular features of the t(14;18) translocation were found in virtually all follicular neoplasms and about 28 percent of diffuse large-cell lymphomas. No changes in bcl-2 were found in several other subtypes of Hodgkin's and non-Hodgkin's lymphomas, including those previously suggested to originate from follicular-center cells and those about which cytogenetic data have been difficult to obtain. Our findings suggest a close pathogenetic relation between bcl-2 and a large group of non-Hodgkin's lymphomas, both with and without a follicular morphology. The methods employed in this study may be useful in improving the accuracy of diagnosis and subclassification of malignant lymphomas. (N Engl J Med 1987; 317:1185–9.)