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Nucleic Acids Research, 1989, Vol. 17, No. 1 1-10
© 1989

MOLECULAR BIOLOGY

Nucleotide sequence of both reciprocal translocation junction regions in a patient with Ph positive acute lymphoblastic leukaemia, with a breakpoint within the first intron of the BCR gene

M.J.M. van der Feltz+,*, M.K.K. Shivji, P.B. Allen, N. Heisterkamp1, J. Groffen1 and L.M. Wiedemann

Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories 237 Fulham Road, London, SW3 6JB, UK 1Childrens Hospital of Los Angeles 4650 Sunset Boulevard, Los Angeles, CA 90027, USA

*To whom correspondence should be addressed

Received November 2, 1988. Accepted December 5, 1988.

Breakpoints on chromosome 22 in the translocation t(9;22) found in Philadelphia positive acute lymphoblastic leukaemia patients fall within two categories. In the first the breakpoint is localized within the breakpoint cluster region of the BCR gene, analogous to the chromosome 22 breakpoint in chronic myeloid leukaemia. The second category has a breakpoint 5' of this area, but still within the BCR gene. We have previously shown that these breakpoints occur within the first intron of the BCR gene and cloned the 9q+ junction from such a patient. We have now determined the sequences around the breakpoints on both translocation partners from this patient as well as the germline regions. The chromosome 9 ABL sequence around the breakpoint shows homology to the consensus Alu sequence whereas the chromosome 22 BCR sequence does not. At the junction there is a 6 bp duplication of the chromosome 22 sequence which is present both in the 9q+ and in the 22q– translocation products. Possible mechanisms for the generation of the translocation are discussed.

+Present address: Dr Daniel den Hoed Cancer Center, PO Box 5201, 3008 AE Rotterdam, The Netherlands


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