PMID- 9446660 OWN - NLM STAT- MEDLINE DCOM- 19980218 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 91 IP - 3 DP - 1998 Feb 1 TI - Application of interphase fluorescence in situ Hybridization for the detection of the Burkitt translocation t(8;14)(q24;q32) in B-cell lymphomas. PG - 984-90 AB - The translocation t(8;14)(q24;q32) is the characteristic chromosomal aberration of Burkitt's-type lymphomas and leukemias (BLs). On the molecular level, the t(8;14) juxtaposes the c-myc gene in 8q24 next to the IgH locus in 14q32, resulting in overexpression of the transcription factor c-Myc. The detection of a t(8;14) is a major aim in the diagnostic process of all patients with high-grade B-cell lymphomas because treatment strategies differ between BL and other high-grade lymphomas. As chromosome analyses are sometimes hampered by the low yield or poor quality of metaphase spreads and as the application of molecular genetic techniques is limited by the distribution of the 8q24 breakpoints over a region of about some hundred kilobases, we set out to establish an interphase fluorescence in situ hybridization (FISH) assay for the detection of the t(8;14). A cosmid probe hybridizing to the IgH constant region in 14q32 was combined with a differently labeled probe of pooled cosmid clones spanning the c-myc locus in 8q24. Interphase nuclei lacking a t(8;14) show two separated signals corresponding to each probe, whereas interphase nuclei carrying a t(8;14) display a split of the c-myc probe and a colocalization of at least one of the splitted signals with the IgH probe. Based on the results of extensive control studies, the cutoff level for this stringent (type I) criteria was set at 2%. Additionally, colocalization of at least one c-myc signal with one IgH signal alone (without signal split for the c-myc probe) was used as a less stringent (type II) criteria with a cutoff limit of 11%. Nine BLs and one Burkitt-like lymphoma were investigated by this approach. Cytogenetically, all tumors contained a translocation t(8;14)(q24;q32) except for one BL, in which cytogenetic analysis had failed. In interphase FISH, all lymphomas and leukemias met the less stringent criteria for the diagnosis of the t(8;14). Additionally, in all tumors but the Burkitt-like lymphoma, a t(8;14) could be diagnosed according to the stringent criteria. The percentage of cells found to harbor the t(8;14) by FISH ranged from 4.3% to 100%. Comparison of cytogenetic and FISH results revealed a significantly lower percentage of t(8;14)+ interphase nuclei than metaphase cells (P = .004). In conclusion, the described FISH assay provides a feasible and sensitive tool for the routine detection of the translocation t(8;14) in interphase cells which might also offer new insights into the biology of high-grade B-cell lymphomas. FAU - Siebert, R AU - Siebert R AD - Department of Human Genetics, University of Kiel, Germany. FAU - Matthiesen, P AU - Matthiesen P FAU - Harder, S AU - Harder S FAU - Zhang, Y AU - Zhang Y FAU - Borowski, A AU - Borowski A FAU - Zuhlke-Jenisch, R AU - Zuhlke-Jenisch R FAU - Metzke, S AU - Metzke S FAU - Joos, S AU - Joos S FAU - Weber-Matthiesen, K AU - Weber-Matthiesen K FAU - Grote, W AU - Grote W FAU - Schlegelberger, B AU - Schlegelberger B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 SB - IM MH - Adult MH - Burkitt Lymphoma/*genetics MH - Child MH - *Chromosomes, Human, Pair 14 MH - *Chromosomes, Human, Pair 8 MH - Female MH - Humans MH - *In Situ Hybridization, Fluorescence MH - Interphase MH - Male MH - Middle Aged MH - *Translocation, Genetic EDAT- 1998/02/03 00:00 MHDA- 1998/02/03 00:01 CRDT- 1998/02/03 00:00 PHST- 1998/02/03 00:00 [pubmed] PHST- 1998/02/03 00:01 [medline] PHST- 1998/02/03 00:00 [entrez] AID - S0006-4971(20)55356-1 [pii] PST - ppublish SO - Blood. 1998 Feb 1;91(3):984-90.