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
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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