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Blood, 1 February 2005, Vol. 105, No. 3, pp. 1329-1336. Prepublished online as a Blood First Edition Paper on September 21, 2004; DOI 10.1182/blood-2004-05-1852. This Article Full Text (PDF) All Versions of this Article: 2004-05-1852v1 105/3/1329    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 Soulier, J. Articles by Gluckman, E. Search for Related Content PubMed PubMed Citation Articles by Soulier, J. Articles by Gluckman, E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 14, 2004 Accepted September 9, 2004 Detection of somatic mosaicism and classification of Fanconi Anemia patients by analysis of the FA/BRCA pathway Jean Soulier*, Thierry Leblanc, Jerome Larghero, Helene Dastot, Akiko Shimamura, Philippe Guardiola, Helene Esperou, Christele Ferry, Charlotte Jubert, Jean-Paul Feugeas, Annie Henri, Antoine Toubert, Gerard Socie, Andre Baruchel, Francois Sigaux, Alan D D'Andrea, and Eliane Gluckman Laboratoire Central d'Hematologie et INSERM U462, Institut Universitaire d'Hematologie (IUH), Hopital Saint-Louis, Paris, France Service d'Hematologie Pediatrique, Institut Universitaire d'Hematologie (IUH), Hopital Saint-Louis, Paris, France Unite de Therapie Cellulaire, Institut Universitaire d'Hematologie (IUH), Hopital Saint-Louis, Paris, France Department of Pediatric Oncology, Dana Farber Cancer Institute, Children's Hospital Boston and Harvard Medical School, Boston, MA, USA Laboratoire Central d'Hematologie et INSERM U462, Institut Universitaire d'Hematologie (IUH), Hopital Saint-Louis, Paris, France; Service de Greffe de Moelle Osseuse, Institut Universitaire d'Hematologie (IUH), Hopital Saint-Louis, Paris, France Service de Greffe de Moelle Osseuse, Institut Universitaire d'Hematologie (IUH), Hopital Saint-Louis, Paris, France Laboratoire de Therapie Genique Hematologique, Institut Universitaire d'Hematologie (IUH), Hopital Saint-Louis, Paris, France Laboratoire d'Immunogenetique Humaine, Institut Universitaire d'Hematologie (IUH), Hopital Saint-Louis, Paris, France * Corresponding author; email: jsoulier{at}chu-stlouis.fr. Fanconi anemia (FA) is characterized by congenital abnormalities, bone marrow failure, chromosome fragility, and cancer susceptibility. Eight FA-associated genes have been identified so far, the products of which function in the FA/BRCA pathway. A key event in the pathway is the monoubiquitination of the FANCD2 protein, which depends on a multiprotein FA core complex. In a number of patients, spontaneous genetic reversion can correct FA mutations, leading to somatic mosaicism. We here analysed the FA/BRCA pathway in 53 FA patients by FANCD2 immunoblots and chromosome breakage tests. Strikingly, FANCD2 monoubiquitination was detected in peripheral blood lymphocytes (PBL) in 8 patients (15%). FA reversion was further shown in these patients by comparison of primary fibroblasts and PBL. Reversion was associated with higher blood counts and clinical stability or improvement. Once constitutional FANCD2 patterns were determined, patients could be classified based on the level of FA/BRCA pathway disruption, as 'FA core' (upstream inactivation, n=47, 89%), FA-D2 (n=4, 8%), and unidentified downstream group (n=2, 4%). FA-D2 and unidentified group patients were therefore relatively common, and they had more severe congenital phenotypes. These results show that specific analysis of the FA/BRCA pathway, combined with clinical and chromosome breakage data, allows a comprehensive characterization of FA patients. 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] Y. Si, A. C. Pulliam, Y. Linka, S. Ciccone, C. Leurs, J. Yuan, O. Eckermann, S. Fruehauf, S. Mooney, H. Hanenberg, et al. Overnight transduction with foamyviral vectors restores the long-term repopulating activity of Fancc-/- stem cells Blood, December 1, 2008; 112(12): 4458 - 4465. [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] A. Mankad, T. Taniguchi, B. Cox, Y. Akkari, R. K. Rathbun, L. Lucas, G. Bagby, S. Olson, A. D'Andrea, and M. Grompe Natural gene therapy in monozygotic twins with Fanconi anemia Blood, April 15, 2006; 107(8): 3084 - 3090. [Abstract] [Full Text] [PDF] Q. Chen, P. C. Van der Sluis, D. Boulware, L. A. Hazlehurst, and W. S. 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