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Mapping Chromosomal Breakpoints of Burkitt's t(8;14) Translocations Far Upstream of c-myc¹

GSF-Forschungszentrum für Umwelt und Gesundheit GmbH, Institut für Klinische Molekularbiologie und Tumorgenetik, 8000 Munich 70, Germany [S. J., M. H. F., G. W. B.]; Dana-Farber Cancer Institute, Boston, Massachusetts 02115[F. G. H.]; Inserm Unité 173, Hôpital Necker, 75730 Paris, France [B. H.]; Abteilung Klinische Genetik der Universität Ulm, 7900 Ulm, Germany [H. H.]; and Jefferson Cancer Institute, Department of Microbiology and Immunology, Philadelphia, Pennsylvania 19107 [C. M. C.]

² To whom requests for reprints should be addressed, at Deutsches Krebsforschungszentrum, Institut für Virusforschung, Im Neuenheimer Feld 280, 6900 Heidelberg, Germany.

To analyze the region upstream of c-myc, a number of novel probes were established. These were generated by chromosomal walking starting from the breakpoint of the chromosomal translocation of the B-cell line 380 and by cloning the breakpoint of the translocation of the Burkitt lymphoma cell line IARC/BL72. Using the newly isolated probes a detailed physical map of 500 kilobases of the region upstream of c-myc was established applying pulsed-field gel electrophoresis. The chromosomal breakpoint of IARC/BL72 cells was mapped to a site 55 kilobases 5' of c-myc. A region 20 kilobases in length and containing the breakpoints of 380, EW36, P3HR-1, and Daudi cells was identified 170–190 kilobases upstream of c-myc. In addition the HPV18 integration site in HeLa cells was located between 340 and 500 kilobases 5' of c-myc. The probes were used to define the c-myc amplification units in Colo320-HSR and HL60 cells as well as in four cases of small cell lung cancer. Evidence is provided that the amplicon of HL60 cells is discontinuously organized.

¹ Supported by the Deutsche Forschungsgemeinschaft (SFB Schwerpunktprogramm, Bo. 681/1-1) and the Fond der chemischen Industrie, Verband der chemischen Industrie e.V., Frankfurt, Germany.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 6/16/92. Accepted 9/23/92.

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