Cancer Research Cancer Health Disparities Conference 2009  SU2C
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

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 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 Fitzgibbon, J.
Right arrow Articles by Young, B. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fitzgibbon, J.
Right arrow Articles by Young, B. D.
[Cancer Research 65, 9152-9154, October 15, 2005]
© 2005 American Association for Cancer Research


Priority Reports

Association between Acquired Uniparental Disomy and Homozygous Gene Mutation in Acute Myeloid Leukemias

Jude Fitzgibbon, Lan-Lan Smith, Manoj Raghavan, Matthew L. Smith, Silvana Debernardi, Spyros Skoulakis, Debra Lillington, T. Andrew Lister and Bryan D. Young

Cancer Research UK Medical Oncology Laboratory, Barts and the Royal London School of Medicine, Queen Mary College, London, United Kingdom

Requests for reprints: Bryan D. Young, Cancer Research UK Medical Oncology Laboratory, Barts and the Royal London School, Charterhouse Square, United Kingdom. Phone: 44-207-882-6002; Fax: 44-207-882-6002; E-mail: bryan.young{at}cancer.org.uk.

Genome-wide single nucleotide polymorphism analysis has revealed large-scale cryptic regions of acquired homozygosity in the form of segmental uniparental disomy in ~20% of acute myeloid leukemias. We have investigated whether such regions, which are the consequence of mitotic recombination, contain homozygous mutations in genes known to be mutational targets in leukemia. In 7 of 13 cases with uniparental disomy, we identified concurrent homozygous mutations at four distinct loci (WT1, FLT3, CEBPA, and RUNX1). This implies that mutation precedes mitotic recombination which acts as a "second hit" responsible for removal of the remaining wild-type allele, as has recently been shown for the JAK2 gene in myeloproliferative disorders.




This article has been cited by other articles:


Home page
Clin. Cancer Res.Home page
C. S. Walsh, S. Ogawa, D. R. Scoles, C. W. Miller, N. Kawamata, S. A. Narod, H. P. Koeffler, and B. Y. Karlan
Genome-Wide Loss of Heterozygosity and Uniparental Disomy in BRCA1/2-Associated Ovarian Carcinomas
Clin. Cancer Res., December 1, 2008; 14(23): 7645 - 7651.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
P. Virappane, R. Gale, R. Hills, I. Kakkas, K. Summers, J. Stevens, C. Allen, C. Green, H. Quentmeier, H. Drexler, et al.
Mutation of the Wilms' Tumor 1 Gene Is a Poor Prognostic Factor Associated With Chemotherapy Resistance in Normal Karyotype Acute Myeloid Leukemia: The United Kingdom Medical Research Council Adult Leukaemia Working Party
J. Clin. Oncol., November 20, 2008; 26(33): 5429 - 5435.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
J. P. Maciejewski and G. J. Mufti
Whole genome scanning as a cytogenetic tool in hematologic malignancies
Blood, August 15, 2008; 112(4): 965 - 974.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
M. Raghavan, L.-L. Smith, D. M. Lillington, T. Chaplin, I. Kakkas, G. Molloy, C. Chelala, J.-B. Cazier, J. D. Cavenagh, J. Fitzgibbon, et al.
Segmental uniparental disomy is a commonly acquired genetic event in relapsed acute myeloid leukemia
Blood, August 1, 2008; 112(3): 814 - 821.
[Abstract] [Full Text] [PDF]


Home page
haematolHome page
L. Wang, C. Fidler, N. Nadig, A. Giagounidis, M. G. Della Porta, L. Malcovati, S. Killick, N. Gattermann, C. Aul, J. Boultwood, et al.
Genome-wide analysis of copy number changes and loss of heterozygosity in myelodysplastic syndrome with del(5q) using high-density single nucleotide polymorphism arrays
Haematologica, July 1, 2008; 93(7): 994 - 1000.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
B. V. Balgobind, P. Van Vlierberghe, A. M. W. van den Ouweland, H. B. Beverloo, J. N. R. Terlouw-Kromosoeto, E. R. van Wering, D. Reinhardt, M. Horstmann, G. J. L. Kaspers, R. Pieters, et al.
Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis
Blood, April 15, 2008; 111(8): 4322 - 4328.
[Abstract] [Full Text] [PDF]


Home page
haematolHome page
A. Tyybakinoja, E. Elonen, H. Vauhkonen, J. Saarela, and S. Knuutila
Single nucleotide polymorphism microarray analysis of karyotypically normal acute myeloid leukemia reveals frequent copy number neutral loss of heterozygosity
Haematologica, April 1, 2008; 93(4): 631 - 632.
[Full Text] [PDF]


Home page
BloodHome page
L. P. Gondek, R. Tiu, C. L. O'Keefe, M. A. Sekeres, K. S. Theil, and J. P. Maciejewski
Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML
Blood, February 1, 2008; 111(3): 1534 - 1542.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Mohamedali, J. Gaken, N. A. Twine, W. Ingram, N. Westwood, N. C. Lea, J. Hayden, N. Donaldson, C. Aul, N. Gattermann, et al.
Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes
Blood, November 1, 2007; 110(9): 3365 - 3373.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
G. F. Kormoczi, E.-M. Dauber, O. A. Haas, T. J. Legler, F. B. Clausen, G. Fritsch, M. Raderer, C. Buchta, A. L. Petzer, D. Schonitzer, et al.
Mosaicism due to myeloid lineage restricted loss of heterozygosity as cause of spontaneous Rh phenotype splitting
Blood, September 15, 2007; 110(6): 2148 - 2157.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
E. A. H. Neuwirth, M. Honma, and A. J. Grosovsky
Interchromosomal Crossover in Human Cells Is Associated with Long Gene Conversion Tracts
Mol. Cell. Biol., August 1, 2007; 27(15): 5261 - 5274.
[Abstract] [Full Text] [PDF]


Home page
haematolHome page
C. Agueli, R. Basirico, F. Fabbiano, V. Rizzo, L. Cascio, G. Cammarata, A. Marfia, M. La Rosa, S. Mirto, and A. Santoro
Loss of heterozygosity in acute leukemia: evidence of frequent submicroscopic deletions
Haematologica, May 1, 2007; 92(5): 678 - 681.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
T. Akasaka, T. Balasas, L. J. Russell, K.-j. Sugimoto, A. Majid, R. Walewska, E. L. Karran, D. G. Brown, K. Cain, L. Harder, et al.
Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
Blood, April 15, 2007; 109(8): 3451 - 3461.
[Abstract] [Full Text] [PDF]


Home page
Hum Mol GenetHome page
C. P. Kratz, D. Steinemann, C. M. Niemeyer, B. Schlegelberger, E. Koscielniak, U. Kontny, and M. Zenker
Uniparental disomy at chromosome 11p15.5 followed by HRAS mutations in embryonal rhabdomyosarcoma: lessons from Costello syndrome
Hum. Mol. Genet., February 15, 2007; 16(4): 374 - 379.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
K. Mrozek, G. Marcucci, P. Paschka, S. P. Whitman, and C. D. Bloomfield
Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification?
Blood, January 15, 2007; 109(2): 431 - 448.
[Abstract] [Full Text] [PDF]


Home page
CarcinogenesisHome page
C. L. Andersen, C. Wiuf, M. Kruhoffer, M. Korsgaard, S. Laurberg, and T. F. Orntoft
Frequent occurrence of uniparental disomy in colorectal cancer
Carcinogenesis, January 1, 2007; 28(1): 38 - 48.
[Abstract] [Full Text] [PDF]


Home page
ASH Education BookHome page
H. Dohner
Implication of the Molecular Characterization of Acute Myeloid Leukemia
Hematology, January 1, 2007; 2007(1): 412 - 419.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
E. Chapiro, L. Russell, I. Radford-Weiss, C. Bastard, M. Lessard, S. Struski, H. Cave, S. Fert-Ferrer, C. Barin, O. Maarek, et al.
Overexpression of CEBPA resulting from the translocation t(14;19)(q32;q13) of human precursor B acute lymphoblastic leukemia
Blood, November 15, 2006; 108(10): 3560 - 3563.
[Abstract] [Full Text] [PDF]


Home page
J. Mol. Diagn.Home page
D. P. Steensma
JAK2 V617F in Myeloid Disorders: Molecular Diagnostic Techniques and Their Clinical Utility: A Paper from the 2005 William Beaumont Hospital Symposium on Molecular Pathology
J. Mol. Diagn., September 1, 2006; 8(4): 397 - 411.
[Abstract] [Full Text] [PDF]


Home page
Genome ResHome page
D. A. Peiffer, J. M. Le, F. J. Steemers, W. Chang, T. Jenniges, F. Garcia, K. Haden, J. Li, C. A. Shaw, J. Belmont, et al.
High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping
Genome Res., September 1, 2006; 16(9): 1136 - 1148.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
K. Stephens, M. Weaver, K. A. Leppig, K. Maruyama, P. D. Emanuel, M. M. Le Beau, and K. M. Shannon
Interstitial uniparental isodisomy at clustered breakpoint intervals is a frequent mechanism of NF1 inactivation in myeloid malignancies
Blood, September 1, 2006; 108(5): 1684 - 1689.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
B. A. Walker, P. E. Leone, M. W. Jenner, C. Li, D. Gonzalez, D. C. Johnson, F. M. Ross, F. E. Davies, and G. J. Morgan
Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms, and genes important in the pathogenesis of multiple myeloma
Blood, September 1, 2006; 108(5): 1733 - 1743.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
U. Bacher, T. Haferlach, C. Schoch, W. Kern, and S. Schnittger
Implications of NRAS mutations in AML: a study of 2502 patients
Blood, May 15, 2006; 107(10): 3847 - 3853.
[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 © 2005 by the American Association for Cancer Research.