Clinical utilization of high-resolution single nucleotide polymorphism based oligonucleotide arrays in diagnostic studies of pediatric patients with solid tumors

Dougherty, Margaret; Tooke, Laura; Sullivan, Lisa M.; Hákonarson, Hákon; Wainwright, Luanne M.; Biegel, Jaclyn A.

doi:10.1016/j.cancergen.2012.01.014

Cited by 18 publications

(16 citation statements)

References 18 publications

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“…SNP-A genotyping was performed using the Illumina HumanOMNI1-Quad, InfiniumCytoSNP 850K or Human610-Quad BeadChip arrays at the CHOP Center for Applied Genomics as previously described. [13] The array chip used was determined based on the platform that was available within our institution at the time of sample processing. Samples were analyzed for the presence of copy number abnormalities and LOH using GenomeStudio (lllumina), which allows direct visualization of the LogR ratio (LRR) and B allele frequency (BAF) plots.…”

Section: Methodsmentioning

confidence: 99%

Clonal evolution and clinical significance of copy number neutral loss of heterozygosity of chromosome arm 6p in acquired aplastic anemia

et al. 2016

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Acquired aplastic anemia (aAA) results from the T cell-mediated autoimmune destruction of hematopoietic stem cells. Factors predicting response to immune suppression therapy (IST) or development of myelodysplastic syndrome (MDS) are beginning to be elucidated. Our recent data suggest most patients with aAA treated with IST develop clonal somatic genetic alterations in hematopoietic cells. One frequent acquired abnormality is copy-number neutral loss of heterozygosity on chromosome 6p (6p CN-LOH) involving the human leukocyte antigen (HLA) locus. We hypothesized that because 6p CN-LOH clones may arise from selective pressure to escape immune surveillance through deletion of HLA alleles, the development of 6p CN-LOH may affect response to IST. We used single nucleotide polymorphism array genotyping and targeted next-generation sequencing of HLA alleles to assess frequency of 6p CN-LOH, identity of HLA alleles lost through 6p CN-LOH, and impact of 6p CN-LOH on response to IST. 6p CN-LOH clones were present in 11.3% of patients, remained stable over time, and were not associated with development of MDS-defining cytogenetic abnormalities. Notably, no patient with 6p CN-LOH treated with IST achieved a complete response. In summary, clonal 6p CN-LOH in aAA defines a unique subgroup of patients that may provide insights into hematopoietic clonal evolution.

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Section: Methodsmentioning

confidence: 99%

Clonal evolution and clinical significance of copy number neutral loss of heterozygosity of chromosome arm 6p in acquired aplastic anemia

et al. 2016

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“…A total of 87 were newly diagnosed patients, and 14 were patients with recurrent brain tumors. Of the 100 cases included in this cohort, thirteen were previously reported (36). The clinical demographics are shown in Supplementary Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…Visual inspection of the LogR ratio and B allele frequency (BAF) plots were performed using the previously mentioned software tools to identify CNAs and regions of homozygosity (ROH). Criteria for reporting CNAs from our laboratory was previously described (36). Briefly, CNAs that encompassed at least 20 consecutive SNPs were included in the clinical reports.…”

Section: Methodsmentioning

confidence: 99%

“…ROH, including copy-neutral loss of heterozygosity (CN-LOH), were included in the report if they were >5 Mb in size, with exceptions that allowed for the reporting of smaller ROH containing known cancer-associated genes. These reporting criteria were chosen based on previous experience of this laboratory with SNP array analysis of a variety of hematologic and solid tumor cases (36,37). Genomic positions for the Human610-Quad and HumanOmni1-Quad arrays were based on the hg18 (March 2006) and hg19 (February 2009) builds of the human genome sequence, respectively (University of California, Santa Cruz (UCSC), http://genome.ucsc.edu/).…”

Section: Methodsmentioning

confidence: 99%

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Diagnostic application of high resolution single nucleotide polymorphism array analysis for children with brain tumors

et al. 2014

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Single nucleotide polymorphism (SNP) array analysis is currently used as a first tier test for pediatric brain tumors at The Children's Hospital of Philadelphia. The results from 100 consecutive patients are summarized in the present report. Eighty-seven percent of the tumors had at least one pathogenic copy number alteration. Nineteen of 56 low grade gliomas (LGGs) demonstrated a duplication in 7q34, which resulted in a KIAA1549-BRAF fusion. Chromosome band 7q34 deletions, which resulted in a FAM131B-BRAF fusion, were identified in one pilocytic astrocytoma and one dysembryoplastic neuroepithelial tumor (DNT). One ganglioglioma (GG) demonstrated a 6q23.3q26 deletion that was predicted to result in a MYB-QKI fusion. Gains of chromosomes 5, 6, 7, 11, and 20 were seen in a subset of LGGs. Monosomy 6, deletion of 9q and 10q, and an i(17)(q10) were each detected in the medulloblastomas (MBs). Deletions and regions of loss of heterozygosity that encompassed TP53, RB1, CDKN2A/B, CHEK2, NF1, and NF2 were identified in a variety of tumors, which led to a recommendation for germline testing. A BRAF p.Thr599dup or p.V600E mutation was identified by Sanger sequencing in one and five LGGs, respectively, and a somatic TP53 mutation was identified in a fibrillary astrocytoma. No TP53 hot-spot mutations were detected in the MBs. SNP array analysis of pediatric brain tumors can be combined with pathologic examination and molecular analyses to further refine diagnoses, offer more accurate prognostic assessments, and identify patients who should be referred for cancer risk assessment.

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“…The authors state that the ASCAT algorithm adjusted for stromal cell contamination which resulted in more accurate calls in the CNAs than without ASCAT processing. Another study reports ASCAT to be the most appropriate software for analyzing Illumina SNP array data (18). However, a complete analytic pipeline for data integration and analysis was absent in both reports.…”

Section: Discussionmentioning

confidence: 99%

Concordance of copy number alterations using a common analytic pipeline for genome-wide analysis of Illumina and Affymetrix genotyping data: a report from the Children's Oncology Group

et al. 2015

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Copy number alterations (CNAs) are a hallmark of pediatric cancer genomes. An increasing number of research groups use multiple platforms and software packages to detect and analyze CNAs. However, different platforms have experimental and analysis-specific biases that may yield different results. We sought to estimate the concordance of CNAs in children with de novo acute myeloid leukemia between two experimental platforms: Affymetrix SNP 6.0 array and Illumina OmniQuad 2.5 BeadChip. Forty-five paired tumor-remission samples were genotyped on the two platforms and CNAs were estimated from total signal intensity and allelic contrast values using the allele-specific copy number analysis of tumors (ASCAT) algorithm. Both platforms were comparable in detection of CNAs, missing only 2 segments from a total of 42 CNAs (4.6%). Overall, there was an inter-platform agreement of 96% for allele-specific tumor profiles. However, poor quality samples with low signal-to-noise ratios showed a high rate of false positive segments independent of the genotyping platform. These results demonstrate that a common analytic pipeline can be utilized for SNP array data from these two platforms. The customized programming template for the preprocessing, data integration, and analysis is publicly available at https://github.com/AplenCHOP/affyLumCNA.

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Clinical utilization of high-resolution single nucleotide polymorphism based oligonucleotide arrays in diagnostic studies of pediatric patients with solid tumors

Cited by 18 publications

References 18 publications

Clonal evolution and clinical significance of copy number neutral loss of heterozygosity of chromosome arm 6p in acquired aplastic anemia

Clonal evolution and clinical significance of copy number neutral loss of heterozygosity of chromosome arm 6p in acquired aplastic anemia

Diagnostic application of high resolution single nucleotide polymorphism array analysis for children with brain tumors

Concordance of copy number alterations using a common analytic pipeline for genome-wide analysis of Illumina and Affymetrix genotyping data: a report from the Children's Oncology Group

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