Document Detail

Myelodysplasia and leukemia of Fanconi anemia are associated with a specific pattern of genomic abnormalities that includes cryptic RUNX1/AML1 lesions.
MedLine Citation:
PMID:  21325596     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-02-16
Journal Detail:
Title:  Blood     Volume:  117     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-15     Completed Date:  2011-06-21     Revised Date:  2011-07-22    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e161-70     Citation Subset:  AIM; IM    
Team Genome and Cancer, Hematology Laboratory Assistance Publique-Hopitaux de Paris, Saint-Louis Hospital, Paris, France.
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MeSH Terms
Bone Marrow / physiology
Child, Preschool
Core Binding Factor Alpha 2 Subunit / genetics*
Fanconi Anemia / complications,  genetics*
Gene Dosage / genetics
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Genes, Tumor Suppressor
Genomic Instability / genetics*
Leukemia, Myeloid, Acute / etiology,  genetics*
Middle Aged
Myelodysplastic Syndromes / etiology,  genetics*
Polymorphism, Single Nucleotide
Young Adult
Reg. No./Substance:
0/Core Binding Factor Alpha 2 Subunit; 0/RUNX1 protein, human
Comment In:
Blood. 2011 Jun 2;117(22):6047-50   [PMID:  21636719 ]

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