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.

Integration of Genomic and Gene Expression Data of Childhood ALL Without Known Aberrations Identifies Subgroups with Specific Genetic Hallmarks / S., Bungaro; M. C., Dell'Orto; A., Zangrando; D., Basso; T., Gorletta; L., Lo Nigro; A., Leszi; B. D., Young; G., Basso; Bicciato, Silvio; A., Biondi; G. T., Kronnie; G., Cazzaniga. - In: GENES, CHROMOSOMES & CANCER. - ISSN 1045-2257. - STAMPA. - 48(1)(2009), pp. 22-38. [10.1002/gcc.20616]

Integration of Genomic and Gene Expression Data of Childhood ALL Without Known Aberrations Identifies Subgroups with Specific Genetic Hallmarks

BICCIATO, Silvio;
2009

Abstract

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.
48(1)
22
38
Integration of Genomic and Gene Expression Data of Childhood ALL Without Known Aberrations Identifies Subgroups with Specific Genetic Hallmarks / S., Bungaro; M. C., Dell'Orto; A., Zangrando; D., Basso; T., Gorletta; L., Lo Nigro; A., Leszi; B. D., Young; G., Basso; Bicciato, Silvio; A., Biondi; G. T., Kronnie; G., Cazzaniga. - In: GENES, CHROMOSOMES & CANCER. - ISSN 1045-2257. - STAMPA. - 48(1)(2009), pp. 22-38. [10.1002/gcc.20616]
S., Bungaro; M. C., Dell'Orto; A., Zangrando; D., Basso; T., Gorletta; L., Lo Nigro; A., Leszi; B. D., Young; G., Basso; Bicciato, Silvio; A., Biondi; G. T., Kronnie; G., Cazzaniga
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/612653
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