| Myelodysplasia and leukemia of Fanconi anemia are associated with a specific pattern of genomic abnormalities that includes cryptic RUNX1/AML1 lesions. | |
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MedLine Citation:
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PMID: 21325596 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Fanconi anemia (FA) is a genetic condition associated with bone marrow (BM) failure, myelodysplasia (MDS), and acute myeloid leukemia (AML). We studied 57 FA patients with hypoplastic or aplastic anemia (n = 20), MDS (n = 18), AML (n = 11), or no BM abnormality (n = 8). BM samples were analyzed by karyotype, high-density DNA arrays with respect to paired fibroblasts, and by selected oncogene sequencing. A specific pattern of chromosomal abnormalities was found in MDS/AML, which included 1q+ (44.8%), 3q+ (41.4%), -7/7q (17.2%), and 11q- (13.8%). Moreover, cryptic RUNX1/AML1 lesions (translocations, deletions, or mutations) were observed for the first time in FA (20.7%). Rare mutations of NRAS, FLT3-ITD, MLL-PTD, ERG amplification, and ZFP36L2-PRDM16 translocation, but no TP53, TET2, CBL, NPM1, and CEBPα mutations were found. Frequent homozygosity regions were related not to somatic copy-neutral loss of heterozygosity but to consanguinity, suggesting that homologous recombination is not a common progression mechanism in FA. Importantly, the RUNX1 and other chromosomal/genomic lesions were found at the MDS/AML stages, except for 1q+, which was found at all stages. These data have implications for staging and therapeutic managing in FA patients, and also to analyze the mechanisms of clonal evolution and oncogenesis in a background of genomic instability and BM failure. |
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Authors:
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Samuel Quentin; Wendy Cuccuini; Raphael Ceccaldi; Olivier Nibourel; Corinne Pondarre; Marie-Pierre Pagès; Nadia Vasquez; Catherine Dubois d'Enghien; Jérôme Larghero; Régis Peffault de Latour; Vanderson Rocha; Jean-Hugues Dalle; Pascale Schneider; Mauricette Michallet; Gérard Michel; André Baruchel; François Sigaux; Eliane Gluckman; Thierry Leblanc; Dominique Stoppa-Lyonnet; Claude Preudhomme; Gérard Socié; Jean Soulier |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-02-16 |
Journal Detail:
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Title: Blood Volume: 117 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-15 Completed Date: 2011-06-21 Revised Date: 2011-07-22 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: e161-70 Citation Subset: AIM; IM |
Affiliation:
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Team Genome and Cancer, Hematology Laboratory Assistance Publique-Hopitaux de Paris, Saint-Louis Hospital, Paris, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Bone Marrow / physiology Child Child, Preschool Core Binding Factor Alpha 2 Subunit / genetics* Fanconi Anemia / complications, genetics* Female Gene Dosage / genetics Gene Expression Profiling Gene Expression Regulation, Leukemic Genes, Tumor Suppressor Genomic Instability / genetics* Homozygote Humans Leukemia, Myeloid, Acute / etiology, genetics* Male Middle Aged Myelodysplastic Syndromes / etiology, genetics* Polymorphism, Single Nucleotide Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Core Binding Factor Alpha 2 Subunit; 0/RUNX1 protein, human |
| Comments/Corrections | |
Comment In:
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Blood. 2011 Jun 2;117(22):6047-50
[PMID:
21636719
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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