Cancer Research Meeting Calendar Jordan
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
[Cancer Research 59, 4075-4082, August 1, 1999]
© 1999 American Association for Cancer Research
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wiemels, J. L.
Right arrow Articles by Greaves, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wiemels, J. L.
Right arrow Articles by Greaves, M.
[Cancer Research 59, 4075-4082, August 15, 1999]
© 1999 American Association for Cancer Research

Molecular Biology and Genetics

Structure and Possible Mechanisms of TEL-AML1 Gene Fusions in Childhood Acute Lymphoblastic Leukemia1

Joseph L. Wiemels2 and Mel Greaves

Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom

TEL-AML1 gene fusion derived by chromosomal translocation is a common acquired genetic lesion in pediatric cancer that is present in ~25% of B-cell precursor acute lymphoblastic leukemias, and recent evidence suggests that this recombination event may initiate leukemogenesis prenatally during fetal hemopoiesis. Analysis of the DNA sequence and structure surrounding the breakpoints may reveal clues to their formation. A long-distance inverse PCR strategy was used to amplify TEL-AML1 genomic fusion sequences from diagnostic DNA from nine patients. Breakpoints were scattered within the 14 kb of intronic DNA between exons 5 and 6 of TEL and in two putative cluster regions within AML1 intron 1. Fusion sequences exhibited characteristic signs of nonhomologous end joining, including microhomologies at the end points, and small deletions and duplications. DNA sequences near the breakpoints did not reveal any consistent characteristic signal sequences of the V(D)J recombinase, topoisomerase II consensus sites, or other sequence motifs associated with recombination. However, several translocations occurred near a repeat region of TEL that was found to be highly polymorphic. This region was cloned and found in nuclease sensitivity assays to exhibit paranemic structures, which may have contributed to DNA breakage or illegitimate recombination. The data are compatible with the possibility that TEL-AML1 translocations occur by nonhomologous recombination involving imprecise, constitutive repair processes following DNA double-strand breaks.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
J. L. Wiemels, J. Hofmann, M. Kang, R. Selzer, R. Green, M. Zhou, S. Zhong, L. Zhang, M. T. Smith, C. Marsit, et al.
Chromosome 12p Deletions in TEL-AML1 Childhood Acute Lymphoblastic Leukemia Are Associated with Retrotransposon Elements and Occur Postnatally
Cancer Res., December 1, 2008; 68(23): 9935 - 9944.
[Abstract] [Full Text] [PDF]

Home page
 J Natl Cancer Inst MonogrHome page
J. Wiemels
Chromosomal Translocations in Childhood Leukemia: Natural History, Mechanisms, and Epidemiology
J Natl Cancer Inst Monographs, July 1, 2008; 2008(39): 87 - 90.
[Abstract] [Full Text] [PDF]

Home page
 aacredbookHome page
P. Vineis and F. Perera
Molecular Epidemiology and Biomarkers in Etiologic Cancer Research: The New in Light of the Old
Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 547 - 567.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
P. Vineis and F. Perera
Molecular Epidemiology and Biomarkers in Etiologic Cancer Research: The New in Light of the Old
Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 1954 - 1965.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. Zuna, A. M. Ford, M. Peham, N. Patel, V. Saha, C. Eckert, J. Kochling, R. Panzer-Grumayer, J. Trka, and M. Greaves
TEL Deletion Analysis Supports a Novel View of Relapse in Childhood Acute Lymphoblastic Leukemia
Clin. Cancer Res., August 15, 2004; 10(16): 5355 - 5360.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
X. Yu and A. Gabriel
Reciprocal Translocations in Saccharomyces cerevisiae Formed by Nonhomologous End Joining
Genetics, February 1, 2004; 166(2): 741 - 751.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
X. Yu and A. Gabriel
Ku-Dependent and Ku-Independent End-Joining Pathways Lead to Chromosomal Rearrangements During Double-Strand Break Repair in Saccharomyces cerevisiae
Genetics, March 1, 2003; 163(3): 843 - 856.
[Abstract] [Full Text] [PDF]

Home page
 ASH Education BookHome page
W. L. Carroll, D. Bhojwani, D.-J. Min, E. Raetz, M. Relling, S. Davies, J. R. Downing, C. L. Willman, and J. C. Reed
Pediatric Acute Lymphoblastic Leukemia
Hematology, January 1, 2003; 2003(1): 102 - 131.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. L. Wiemels, B. C. Leonard, Y. Wang, M. R. Segal, S. P. Hunger, M. T. Smith, V. Crouse, X. Ma, P. A. Buffler, and S. R. Pine
Site-specific translocation and evidence of postnatal origin of the t(1;19) E2A-PBX1 fusion in childhood acute lymphoblastic leukemia
PNAS, November 12, 2002; 99(23): 15101 - 15106.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Mori, S. M. Colman, Z. Xiao, A. M. Ford, L. E. Healy, C. Donaldson, J. M. Hows, C. Navarrete, and M. Greaves
Chromosome translocations and covert leukemic clones are generated during normal fetal development
PNAS, June 11, 2002; 99(12): 8242 - 8247.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. J. Gaymes, G. J. Mufti, and F. V. Rassool
Myeloid Leukemias Have Increased Activity of the Nonhomologous End-Joining Pathway and Concomitant DNA Misrepair that Is Dependent on the Ku70/86 Heterodimer
Cancer Res., May 1, 2002; 62(10): 2791 - 2797.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
V. J. Weston, C. M. McConville, J. R. Mann, P. J. Darbyshire, S. Lawson, J. Gordon, P. A. H. Moss, A. Malcolm, R. Taylor, and T. Stankovic
Molecular Analysis of Single Colonies Reveals a Diverse Origin of Initial Clonal Proliferation in B-Precursor Acute Lymphoblastic Leukemia that Can Precede the t(12;21) Translocation
Cancer Res., December 1, 2001; 61(23): 8547 - 8553.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. G. Blanco, T. Dervieux, M. J. Edick, P. K. Mehta, J. E. Rubnitz, S. Shurtleff, S. C. Raimondi, F. G. Behm, C.-H. Pui, and M. V. Relling
Molecular emergence of acute myeloid leukemia during treatment for acute lymphoblastic leukemia
PNAS, August 28, 2001; 98(18): 10338 - 10343.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. M. Ford, K. Fasching, E. R. Panzer-Grumayer, M. Koenig, O. A. Haas, and M. F. Greaves
Origins of "late" relapse in childhood acute lymphoblastic leukemia with TEL-AML1 fusion genes
Blood, August 1, 2001; 98(3): 558 - 564.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. T. Maia, A. M. Ford, G. R. Jalali, C. J. Harrison, G. M. Taylor, O. B. Eden, and M. F. Greaves
Molecular tracking of leukemogenesis in a triplet pregnancy
Blood, July 15, 2001; 98(2): 478 - 482.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Eguchi-Ishimae, M. Eguchi, E. Ishii, S. Miyazaki, K. Ueda, N. Kamada, and S. Mizutani
Breakage and fusion of the TEL (ETV6) gene in immature B lymphocytes induced by apoptogenic signals
Blood, February 1, 2001; 97(3): 737 - 743.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J.-W. Vaandrager, E. Schuuring, K. Philippo, and P. M. Kluin
V(D)J recombinase-mediated transposition of the BCL2 gene to the IGH locus in follicular lymphoma
Blood, September 1, 2000; 96(5): 1947 - 1952.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. L. Wiemels, R. N. Smith, G. M. Taylor, O. B. Eden, F. E. Alexander, M. F. Greaves, and United Kingdom Childhood Cancer Study Investigator
Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia
PNAS, March 27, 2001; 98(7): 4004 - 4009.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.