Detection of the t(14; 18) chromosomal translocation by interphase cytogenetics with yeast-artificial-chromosome probes in follicular lymphoma and nonneoplastic lymphoproliferation

Purpose: The aim of this study was to establish a fluorescence in situ hybridization (FISH) technique for the detection of t(14; 18)(q32;q21), characteristic for follicular lymphoma (Kiel classification: centroblastic centrocytic [cb-cc] lymphoma). Materials and Methods: After the FISH system had been established, parallel studies of lymph node biopsy specimens from 30 patients with cb-cc lymphoma and from 32 patients with nonneoplastic lymphoproliferation were performed by means of chromosome analysis, polymerase chain reaction (PCR), and FISH analysis. Two differently labeled yeast-artificial-chromosome (YAC) probes that contained the entire bcl-2 gene and the C-region of the immunoglobulin H (IgH) gene, respectively, were used to detect t(14; 18) by FISH. Results: The presence of the translocation is indicated by a red(Cy3)/green (fluorescien isothiocyanate [FITC]) double signal, which corresponds to the IgH/bcl-2 fusion gene, whereas in normal cells the signals are separate. Control studies showed that the double signal is visible in less than 1% of normal cells. FISH analysis was able to identify the t(14; 18) in all cases of cb-cc lymphoma we studied. All bcl-2 breakpoints can be detected, Combined immunophenotyping and interphase cytogenetics demonstrated that t(14; 18) was restricted to CD22(+) B lymphocytes and never occurred in CD3(+) T lymphocytes. In four of 32 cases of nonneoplastic lymphoproliferation, t(14; 18)was also detected. Conclusion: FISH turned out to be the most sensitive method to detect t(14; 18). Our FISH results confirm PCR data from other groups that found evidence for the presence of t(14;18) in nonneoplastic lymphoproliferation. It needs to be determined whether, in morphologically nonneoplastic processes, t(14; 18) is associated with an increased risk for the development of non-Hodgkin's lymphoma. (C) 1996 by American Society of Clinical Oncology.