Pediatric acute lymphoblastic leukemia (ALL) comprises genetically distinct subtypes. However, 25% of cases still lack defined genetic hallmarks. To identify genomic aberrancies in childhood ALL patients nonclassifiable by conventional methods, we performed a single nuclecitide polymorphisms (SNP) array-based genomic analysis of leukemic cells from 29 cases. The vast majority of cases analyzed (19/24, 79%) showed genomic abnormalities; at least one of them affected either genes involved in cell cycle regulation or in B-cell development. The most relevant abnormalities were CDKN2A/9p21 deletions (7/24, 29%), ETV6 (TEL)/12p 13 deletions (3/24, 12%), and intrachromosomal amplifications of chromosome 21 (iAMP21) (3/24, 12%). To identify variation in expression of genes directly or indirectly affected by recurrent genomic alterations, we integrated genomic and gene expression data generated by microarray analyses of the same samples. SMAD 1 emerged as a down-regulated gene in CDKN2A homozygous deleted cases compared with nondeleted. The JAG1 gene, encoding the jagged I ligand of the Notch receptor, was among a list of differentially expressed (up-regulated) genes in ETV6-deleted cases. Our findings demonstrate that integration of genomic analysis and gene expression profiling can identify genetic lesions undetected by routine methods and potential novel pathways involved in B-progenitor ALL pathogenesis.
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|Data di pubblicazione:||2009|
|Titolo:||Integration of Genomic and Gene Expression Data of Childhood ALL Without Known Aberrations Identifies Subgroups with Specific Genetic Hallmarks|
|Autori:||S. Bungaro; M.C. Dell'Orto; A. Zangrando; D. Basso; T. Gorletta; L. Lo Nigro; A. Leszi; B.D. Young; G. Basso; S. Bicciato; A. Biondi; G.T. Kronnie; G. Cazzaniga|
|Digital Object Identifier (DOI):||10.1002/gcc.20616|
|Appare nelle tipologie:||Articolo su rivista|
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