dChipSNP: significance curve and clustering of SNP-array-based loss-of-heterozygosity data

Lin, Ming Gang; Wei, Lee‐Jen; Sellers, William R.; Lieberfarb, Marshall; Wong, Wing Hung; Li, Cheng

doi:10.1093/bioinformatics/bth069

Cited by 340 publications

(316 citation statements)

References 14 publications

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“…20 Arrays were normalized against the array with median overall intensity (Baseline array) using the invariant set normalization method. 21 Probe set signal intensity was obtained by using a model based on expression index (PM/MM) method.…”

Section: Resultsmentioning

confidence: 99%

New pattern of EGFR amplification in glioblastoma and the relationship of gene copy number with gene expression profile

et al. 2010

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Gene amplification is a process that is characterized by an increase in the copy number of a restricted region in a chromosome arm, and is frequently associated with an overexpression of the corresponding amplified gene. Amplified DNA can be organized either as extrachromosomal elements, repeated units at a single locus or scattered throughout the genome. The amplification of the gene for epidermal growth factor receptor (EGFR) is a common finding in glioblastomas and the amplified gene copies appears as double minutes. The aim of this study was to investigate the different patterns of EGFR amplification in 40 cases of glioblastoma using FISH analysis in metaphases and paraffin sections, and to investigate the relationship of gene copy number with gene expression profile. The analysis of copy number alterations of EGFR was validated by quantitative PCR and SNP microarrays. We observed that in 42% of the cases, the type of amplification of EGFR was as double minute chromosomes. In addition, we detected another type of amplification, with extra copies of EGFR inserted in different loci of chromosome 7, present in 28% of cases. In this form of amplification, the number of copies is small, and the percentage of cells with EGFR amplification is rarely more than 15%. This model of amplification could correspond to a variant of the insertion mechanism, or a consequence of a process of duplication. Our results suggest that this mechanism could represent an early stage of amplification in glioblastomas. Overall, we found a close correlation between EGFR gene copy-number alterations and the level of EGFR protein expression. However, all cases with a high level of mRNA exhibited strong expression for the EGFR protein, and most cases with a low level of mRNA showed no overexpression of EGFR protein.

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Section: Resultsmentioning

confidence: 99%

New pattern of EGFR amplification in glioblastoma and the relationship of gene copy number with gene expression profile

et al. 2010

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“…Using the previously described dChipSNP algorithm (Lin et al, 2004;Zhao et al, 2004;Garraway et al, 2005), seven of the 63 tumors were predicted to have only one copy of the 53BP1 gene, detected with the SNP_A-1659281 (rs10518815) and SNP_A-1657986 (rs555252) probes.…”

Section: Resultsmentioning

confidence: 99%

“…The scanned data from the SNP arrays were processed with dChipSNP software (Li and Wong, 2001;Lin et al, 2004). After normalization, the intensity of each SNP in each tumor sample was rescaled using the average intensity of the same SNP across the 180 normal samples (Li and Wong, 2001).…”

Section: Samplesmentioning

confidence: 99%

“…After normalization, the intensity of each SNP in each tumor sample was rescaled using the average intensity of the same SNP across the 180 normal samples (Li and Wong, 2001). A genome-wide view of inferred copy number was generated by a Hidden Markov Model with dChipSNP as described previously (Lin et al, 2004;Zhao et al, 2004;Garraway et al, 2005).…”

Section: Samplesmentioning

confidence: 99%

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Integrative analysis reveals 53BP1 copy loss and decreased expression in a subset of human diffuse large B-cell lymphomas

et al. 2007

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p53-Binding protein 1 (53BP1) encodes a critical checkpoint protein that localizes to sites of DNA double-strand breaks (DSBs) and participates in DSB repair. Mice that are 53bp1 deficient or hemizygous have an increased incidence of lymphoid malignancies. However, 53BP1 abnormalities in primary human tumors have not been described. By combining high-density single nucleotide polymorphism (HD SNP) array data and gene expression profiles, we found 9 of 63 newly diagnosed human diffuse large B-cell lymphomas (DLBCLs) with single copy loss of the chromosome 15q15 region including the 53BP1 locus; these nine tumors also had significantly lower levels of 53BP1 transcripts. 53BP1 single copy loss found with the HD SNP array platform was subsequently confirmed by fluorescence in situ hybridization. These studies highlight the role of 53BP1 copy loss in primary human DLBCLs and the value of integrative analyses in detecting this genetic lesion in human tumors.

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“…For verification of the mutational impact on the splice donor site of exon 9, target cDNA was amplified with primers ETPR06 and ETPR07 from the Exontrap kit and analyzed by Sanger sequencing with ChromasLite software (Technelysium) and the UCSC Genome Browser. 16,17 Homozygosity Mapping Both affected individuals of the Tunisian family were genotyped on Affymetrix GeneChip Human Mapping 250K NspI arrays with dCHIP software 18 at the Center for Medical Research at the Medical University of Graz.…”

Section: Exon Trapping Assaymentioning

confidence: 99%

CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays

Windpassinger

Piard

Bonnard

et al. 2017

The American Journal of Human Genetics

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In five separate families, we identified nine individuals affected by a previously unidentified syndrome characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delays. Using homozygosity mapping, array CGH, and exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease. CDK10 is a protein kinase that partners with cyclin M to phosphorylate substrates such as ETS2 and PKN2 in order to modulate cellular growth. To validate and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mice. Homozygous Cdk10-knockout mice died postnatally with severe growth retardation, skeletal defects, and kidney and lung abnormalities, symptoms that partly resemble the disease's effect in humans. Fibroblasts derived from affected individuals and Cdk10-knockout mouse embryonic fibroblasts (MEFs) proliferated normally; however, Cdk10-knockout MEFs developed longer cilia. Comparative transcriptomic analysis of mutant and wild-type mouse organs revealed lipid metabolic changes consistent with growth impairment and altered ciliogenesis in the absence of CDK10. Our results document the CDK10 loss-of-function phenotype and point to a function for CDK10 in transducing signals received at the primary cilia to sustain embryonic and postnatal development.

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dChipSNP: significance curve and clustering of SNP-array-based loss-of-heterozygosity data

Abstract: The breast cancer data are provided by Andrea L. Richardson, Zhigang C. Wang and James D. Iglehart.

Cited by 340 publications

References 14 publications

New pattern of EGFR amplification in glioblastoma and the relationship of gene copy number with gene expression profile

New pattern of EGFR amplification in glioblastoma and the relationship of gene copy number with gene expression profile

Integrative analysis reveals 53BP1 copy loss and decreased expression in a subset of human diffuse large B-cell lymphomas

CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays

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