SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on August 29, 2002; DOI 10.1182/blood-2002-05-1399. This Article Full Text (PDF) All Versions of this Article: 2002-05-1399v1 100/13/4649    most recent Alert me when this article is cited Alert me if a correction is posted 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 Shimamura, A. Articles by D'Andrea, A. D Search for Related Content PubMed PubMed Citation Articles by Shimamura, A. Articles by D'Andrea, A. D Social Bookmarking                   What's this? Submitted May 23, 2002 Accepted July 15, 2002 A novel diagnostic screen for defects in the Fanconi anemia pathway Akiko Shimamura*, Rocio Montes de Oca, John L Svenson, Nicholas Haining, Lisa A Moreau, David G Nathan, and Alan D D'Andrea Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA * Corresponding author; email: Akiko_Shimamura{at}dfci.harvard.edu. Fanconi anemia (FA) is an autosomal recessive chromosomal instability syndrome characterized by congenital abnormalities, progressive bone marrow failure, and cancer predisposition. Although FA patients are candidates for bone marrow transplant or gene therapy, their phenotypic heterogeneity can delay or obscure diagnosis. The current diagnostic test for FA consists of cytogenetic quantitation of chromosomal breakage in response to diepoxybutane (DEB) or mitomycin C (MMC). Recent studies have elucidated a biochemical pathway for Fanconi Anemia that culminates in the monoubiquitination of the FANCD2 protein. In the current study, we develop a new rapid diagnostic and subtyping FA assay amenable for screening broad populations at risk for FA. Primary lymphocytes were assayed for FANCD2 monoubiquitination by immunoblot. The absence of the monoubiquitinated FANCD2 isoform correlated with the diagnosis of FA by DEB testing in 11 known FA patients, 37 patients referred for possible FA, and 29 normal controls. Monoubiquitination of FANCD2 was normal in other bone marrow failure syndromes and chromosomal breakage syndromes. A combination of retroviral gene transfer and FANCD2 immunoblotting provides a rapid subtyping assay for newly diagnosed FA patients. These new FA screening assays would allow efficient testing of broad populations at risk. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. O. Pinto, T. Leblanc, D. Chamousset, G. Le Roux, B. Brethon, B. Cassinat, J. Larghero, J.-P. de Villartay, D. Stoppa-Lyonnet, A. Baruchel, et al. Diagnosis of Fanconi anemia in patients with bone marrow failure Haematologica, April 1, 2009; 94(4): 487 - 495. [Abstract] [Full Text] [PDF] J. Antonio Casado, E. Callen, A. Jacome, P. Rio, M. Castella, S. Lobitz, T. Ferro, A. Munoz, J. Sevilla, A. Cantalejo, et al. A comprehensive strategy for the subtyping of patients with Fanconi anaemia: conclusions from the Spanish Fanconi Anemia Research Network J. Med. Genet., April 1, 2007; 44(4): 241 - 249. [Abstract] [Full Text] [PDF] T. Pejovic, J. E. Yates, H. Y. Liu, L. E. Hays, Y. Akkari, Y. Torimaru, W. Keeble, R. K. Rathbun, W. H. Rodgers, A. E. Bale, et al. Cytogenetic instability in ovarian epithelial cells from women at risk of ovarian cancer. Cancer Res., September 15, 2006; 66(18): 9017 - 9025. [Abstract] [Full Text] [PDF] T. Taniguchi and A. D. D'Andrea Molecular pathogenesis of Fanconi anemia: recent progress Blood, June 1, 2006; 107(11): 4223 - 4233. [Abstract] [Full Text] [PDF] A. M. Gurtan, P. Stuckert, and A. D. D'Andrea The WD40 Repeats of FANCL Are Required for Fanconi Anemia Core Complex Assembly J. Biol. Chem., April 21, 2006; 281(16): 10896 - 10905. [Abstract] [Full Text] [PDF] A. Shimamura Inherited Bone Marrow Failure Syndromes: Molecular Features Hematology, January 1, 2006; 2006(1): 63 - 71. [Abstract] [Full Text] [PDF] K. M. Austin, R. J. Leary, and A. Shimamura The Shwachman-Diamond SBDS protein localizes to the nucleolus Blood, August 15, 2005; 106(4): 1253 - 1258. [Abstract] [Full Text] [PDF] R. Montes de Oca, P. R. Andreassen, S. P. Margossian, R. C. Gregory, T. Taniguchi, X. Wang, S. Houghtaling, M. Grompe, and A. D. D'Andrea Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatin Blood, February 1, 2005; 105(3): 1003 - 1009. [Abstract] [Full Text] [PDF] J. Soulier, T. Leblanc, J. Larghero, H. Dastot, A. Shimamura, P. Guardiola, H. Esperou, C. Ferry, C. Jubert, J.-P. Feugeas, et al. Detection of somatic mosaicism and classification of Fanconi anemia patients by analysis of the FA/BRCA pathway Blood, February 1, 2005; 105(3): 1329 - 1336. [Abstract] [Full Text] [PDF] B. P. Alter Bone Marrow Failure: A Child Is Not Just a Small Adult (But an Adult Can Have a Childhood Disease) Hematology, January 1, 2005; 2005(1): 96 - 103. [Abstract] [Full Text] [PDF] G. Narayan, H. Arias-Pulido, S. V. Nandula, K. Basso, D. D. Sugirtharaj, H. Vargas, M. Mansukhani, J. Villella, L. Meyer, A. Schneider, et al. Promoter Hypermethylation of FANCF: Disruption of Fanconi Anemia-BRCA Pathway in Cervical Cancer Cancer Res., May 1, 2004; 64(9): 2994 - 2997. [Abstract] [Full Text] [PDF] B. Hirsch, A. Shimamura, L. Moreau, S. Baldinger, M. Hag-alshiekh, B. Bostrom, S. Sencer, and A. D. D'Andrea Association of biallelic BRCA2/FANCD1 mutations with spontaneous chromosomal instability and solid tumors of childhood Blood, April 1, 2004; 103(7): 2554 - 2559. [Abstract] [Full Text] [PDF] A. Shimamura and A. D. D'Andrea Subtyping of Fanconi anemia patients: implications for clinical management Blood, November 1, 2003; 102(9): 3459 - 3459. [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020