Panhandle and reverse-panhandle PCR enable cloning of der(11) and der(other) genomic breakpoint junctions of MLL translocations and identify complex translocation of MLL, AF-4, and CDK6

Proceedings of the National Academy of Sciences of the United States of America
Leslie J RaffiniC A Felix

Abstract

We used panhandle PCR to clone the der(11) genomic breakpoint junction in three leukemias with t(4;11) and devised reverse-panhandle PCR to clone the breakpoint junction of the other derivative chromosome. This work contributes two elements to knowledge on MLL translocations. First is reverse-panhandle PCR for cloning breakpoint junctions of the other derivative chromosomes, sequences of which are germane to understanding the MLL translocation process. The technique revealed duplicated sequences in one case of infant acute lymphoblastic leukemia (ALL) and small deletions in a case of treatment-related ALL. The second element is discovery of a three-way rearrangement of MLL, AF-4, and CDK6 in another case of infant ALL. Cytogenetic analysis was unsuccessful at diagnosis, but suggested t(4;11) and del(7)(q21q31) at relapse. Panhandle PCR analysis of the diagnostic marrow identified a breakpoint junction of MLL intron 8 and AF-4 intron 3. Reverse-panhandle PCR identified a breakpoint junction of CDK6 from band 7q21-q22 and MLL intron 9. CDK6 encodes a critical cell cycle regulator and is the first gene of this type disrupted by MLL translocation. Cdk6 is overexpressed or disrupted by translocation in many cancers. The in-frame CDK...Continue Reading

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Citations

Oct 1, 2005·Histochemistry and Cell Biology·Lóránt SzékvölgyiGábor Szabó
Nov 19, 2005·Nature Reviews. Cancer·James M Allan, Lois B Travis
Jul 26, 2012·International Journal of Environmental Research and Public Health·Ian G Cowell, Caroline A Austin
Jan 1, 2005·Proceedings of the National Academy of Sciences of the United States of America·Claus MeyerRolf Marschalek
Sep 15, 2007·Cancer Genetics and Cytogenetics·William T ChoiDean A Lee
May 12, 2009·Pediatric Blood & Cancer·Carolyn A Felix
Apr 22, 2008·British Journal of Haematology·Blaine W RobinsonCarolyn A Felix
Dec 12, 2013·Genes, Chromosomes & Cancer·Kayleigh A SmithCaroline A Austin
Aug 1, 2006·Cancer Genetics and Cytogenetics·Manabu NinomiyaTomoki Naoe
Jul 22, 2006·DNA Repair·Carolyn A FelixNeil Osheroff
Jan 1, 2011·Case Reports in Hematology·Hirotaka TakasakiHeiwa Kanamori
Aug 31, 2004·Genes, Chromosomes & Cancer·Xin Ying SuOlivier A Bernard
Aug 8, 2006·Biotechnology Journal·Claus MeyerRolf Marschalek
Nov 25, 2004·Hematology·D Gary GillilandCarolyn A Felix
Dec 11, 2002·The Journal of Biological Chemistry·Kenneth D BrombergNeil Osheroff

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