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Blood, 1 August 2008, Vol. 112, No. 3, pp. 814-821. Prepublished online as a Blood First Edition Paper on May 19, 2008; DOI 10.1182/blood-2008-01-132431. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-01-132431v1 112/3/814    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Raghavan, M. Articles by Young, B. D. Search for Related Content PubMed PubMed Citation Articles by Raghavan, M. Articles by Young, B. D. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Segmental uniparental disomy is a commonly acquired genetic event in relapsed acute myeloid leukemia Manoj Raghavan1, Lan-Lan Smith1, Debra M. Lillington1, Tracy Chaplin1, Ioannis Kakkas1, Gael Molloy1, Claude Chelala2, Jean-Baptiste Cazier1,3, James D. Cavenagh4, Jude Fitzgibbon1, T. Andrew Lister1, and Bryan D. Young1 1 Medical Oncology Unit and 2 Molecular Pathology Group, Centre for Molecular Oncology, Institute of Cancer, Barts and the London School of Medicine and Dentistry, London; 3 Cancer Research UK Bioinformatics and Biostatistics Service, London; and 4 Department of Haematology Oncology, St Bartholomew's Hospital, London, United Kingdom Despite advances in the curative treatment of acute myeloid leukemia (AML), recurrence will occur in the majority of cases. At diagnosis, acquisition of segmental uniparental disomy (UPD) by mitotic recombination has been reported in 15% to 20% of AML cases, associated with homozygous mutations in the region of loss of heterozygosity. This study aimed to discover if clonal evolution from heterozygous to homozygous mutations by mitotic recombination provides a mechanism for relapse. DNA from 27 paired diagnostic and relapsed AML samples were analyzed using genotyping arrays. Newly acquired segmental UPDs were observed at relapse in 11 AML samples (40%). Six were segmental UPDs of chromosome 13q, which were shown to lead to a change from heterozygosity to homozygosity for internal tandem duplication mutation of FLT3 (FLT3 ITD). Three further AML samples had evidence of acquired segmental UPD of 13q in a subclone of the relapsed leukemia. One patient acquired segmental UPD of 19q that led to homozygosity for a CEBPA mutation 207C>T. Finally, a single patient with AML acquired segmental UPD of chromosome 4q, for which the candidate gene is unknown. We conclude that acquisition of segmental UPD and the resulting homozygous mutation is a common event associated with relapse of AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. V. Tiu, L. P. Gondek, C. L. O'Keefe, J. Huh, M. A. Sekeres, P. Elson, M. A. McDevitt, X. F. Wang, M. J. Levis, J. E. Karp, et al. New Lesions Detected by Single Nucleotide Polymorphism Array-Based Chromosomal Analysis Have Important Clinical Impact in Acute Myeloid Leukemia J. Clin. Oncol., November 1, 2009; 27(31): 5219 - 5226. [Abstract] [Full Text] [PDF] A. M. Mohamedali, A. E. Smith, J. Gaken, N. C. Lea, S. A. Mian, N. B. Westwood, C. Strupp, N. Gattermann, U. Germing, and G. J. Mufti Novel TET2 Mutations Associated With UPD4q24 in Myelodysplastic Syndrome J. Clin. Oncol., August 20, 2009; 27(24): 4002 - 4006. [Abstract] [Full Text] [PDF] S. Meshinchi and F. R. Appelbaum Structural and Functional Alterations of FLT3 in Acute Myeloid Leukemia Clin. Cancer Res., July 1, 2009; 15(13): 4263 - 4269. [Abstract] [Full Text] [PDF] F. Delhommeau, S. Dupont, V. D. Valle, C. James, S. Trannoy, A. Masse, O. Kosmider, J.-P. Le Couedic, F. Robert, A. Alberdi, et al. Mutation in TET2 in Myeloid Cancers N. Engl. J. Med., May 28, 2009; 360(22): 2289 - 2301. [Abstract] [Full Text] [PDF] S. Bea, I. Salaverria, L. Armengol, M. Pinyol, V. Fernandez, E. M. Hartmann, P. Jares, V. Amador, L. Hernandez, A. Navarro, et al. Uniparental disomies, homozygous deletions, amplifications, and target genes in mantle cell lymphoma revealed by integrative high-resolution whole-genome profiling Blood, March 26, 2009; 113(13): 3059 - 3069. [Abstract] [Full Text] [PDF] T. Akagi, L.-Y. Shih, M. Kato, N. Kawamata, G. Yamamoto, M. Sanada, R. Okamoto, C. W. Miller, D.-C. Liang, S. Ogawa, et al. Hidden abnormalities and novel classification of t(15;17) acute promyelocytic leukemia (APL) based on genomic alterations Blood, February 19, 2009; 113(8): 1741 - 1748. [Abstract] [Full Text] [PDF] T. Akagi, S. Ogawa, M. Dugas, N. Kawamata, G. Yamamoto, Y. Nannya, M. Sanada, C. W. Miller, A. Yung, S. Schnittger, et al. Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype Haematologica, February 1, 2009; 94(2): 213 - 223. [Abstract] [Full Text] [PDF]

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