Integration of genomic and gene expression data of childhood ALL without known aberrations identifies subgroups with specific genetic hallmarks
Autor: | Andrea Zangrando, Bryan D. Young, Tatiana Gorletta, Luca Lo Nigro, Andrea Biondi, Giovanni Cazzaniga, Dario Basso, Gertruy te Kronnie, Silvio Bicciato, Giuseppe Basso, Silvia Bungaro, Marta Campo Dell'Orto, Anna Leszl |
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Přispěvatelé: | Bungaro, S, Dell'Orto, M, Zangrando, A, Basso, D, Gorletta, T, Lo Nigro, L, Leszl, A, Young, B, Basso, G, Bicciato, S, Biondi, A, te Kronnie, G, Cazzaniga, G |
Rok vydání: | 2009 |
Předmět: |
Male
Cancer Research Chromosomes Human Pair 21 B-Cell-Specific Activator Protein CDKN2A Genetic Marker Intercellular Signaling Peptides and Protein Serrate-Jagged Proteins Child Membrane Protein Calcium-Binding Protein Oligonucleotide Array Sequence Analysis Genetics Proto-Oncogene Proteins c-et Gene Expression Regulation Leukemic Precursor Cell Lymphoblastic Leukemia-Lymphoma Uniparental disomy Child Preschool Intercellular Signaling Peptides and Proteins Female Chromosome Deletion Human Genetic Markers Adolescent Single-nucleotide polymorphism Biology Chromosome Aberration Polymorphism Single Nucleotide Smad1 Protein medicine Humans Gene Chromosome Aberrations Proto-Oncogene Proteins c-ets Oligonucleotide Array Sequence Analysi Genes p16 Calcium-Binding Proteins PAX5 Transcription Factor Infant Membrane Proteins Repressor Protein Uniparental Disomy medicine.disease Repressor Proteins Gene expression profiling ETV6 Genetic marker Chromosome 21 Gene Deletion Jagged-1 Protein |
Zdroj: | Genes, Chromosomes and Cancer. 48:22-38 |
ISSN: | 1098-2264 1045-2257 |
Popis: | 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 nucleotide 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)/12p13 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. SMAD1 emerged as a down-regulated gene in CDKN2A homozygous deleted cases compared with nondeleted. The JAG1 gene, encoding the Jagged 1 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. © 2008 Wiley-Liss, Inc. |
Databáze: | OpenAIRE |
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