Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation

TY - JOUR

T1 - Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation

AU - Milani, Lili

AU - Lundmark, Anders

AU - Nordlund, Jessica

AU - Kiialainen, Anna

AU - Flaegstad, Trond

AU - Jonmundsson, Gudmundur

AU - Kanerva, Jukka

AU - Schmiegelow, K.

AU - Gunderson, Kevin L

AU - Lönnerholm, Gudmar

AU - Syvänen, Ann-Christine

N1 - Keywords: Adolescent; Alleles; Child; Child, Preschool; CpG Islands; DNA Methylation; DNA, Neoplasm; Gene Expression; Humans; Infant; Polymorphism, Single Nucleotide; Precursor Cell Lymphoblastic Leukemia-Lymphoma; RNA, Neoplasm; Tumor Cells, Cultured

PY - 2008

Y1 - 2008

N2 - To identify genes that are regulated by cis-acting functional elements in acute lymphoblastic leukemia (ALL) we determined the allele-specific expression (ASE) levels of 2, 529 genes by genotyping a genome-wide panel of single nucleotide polymorphisms in RNA and DNA from bone marrow and blood samples of 197 children with ALL. Using a reproducible, quantitative genotyping method and stringent criteria for scoring ASE, we found that 16% of the analyzed genes display ASE in multiple ALL cell samples. For most of the genes, the level of ASE varied largely between the samples, from 1.4-fold overexpression of one allele to apparent monoallelic expression. For genes exhibiting ASE, 55% displayed bidirectional ASE in which overexpression of either of the two SNP alleles occurred. For bidirectional ASE we also observed overall higher levels of ASE and correlation with the methylation level of these sites. Our results demonstrate that CpG site methylation is one of the factors that regulates gene expression in ALL cells.

AB - To identify genes that are regulated by cis-acting functional elements in acute lymphoblastic leukemia (ALL) we determined the allele-specific expression (ASE) levels of 2, 529 genes by genotyping a genome-wide panel of single nucleotide polymorphisms in RNA and DNA from bone marrow and blood samples of 197 children with ALL. Using a reproducible, quantitative genotyping method and stringent criteria for scoring ASE, we found that 16% of the analyzed genes display ASE in multiple ALL cell samples. For most of the genes, the level of ASE varied largely between the samples, from 1.4-fold overexpression of one allele to apparent monoallelic expression. For genes exhibiting ASE, 55% displayed bidirectional ASE in which overexpression of either of the two SNP alleles occurred. For bidirectional ASE we also observed overall higher levels of ASE and correlation with the methylation level of these sites. Our results demonstrate that CpG site methylation is one of the factors that regulates gene expression in ALL cells.

U2 - 10.1101/gr.083931.108

DO - 10.1101/gr.083931.108

M3 - Journal article

C2 - 18997001

SN - 1088-9051

VL - 19

SP - 1

EP - 11

JO - Genome Research

JF - Genome Research

IS - 1

ER -