Copynumber: Efficient algorithms for single- and multi-track copy number segmentation

Nilsen, Gro; Liestøl, Knut; Loo, Peter Van; Vollan, Hans Kristian Moen; Eide, Marianne Brodtkorb; Rueda, Oscar M.; Chin, Suet Feung; Russell, Roslin; Baumbusch, Lars Oliver; Caldas, Carlos; Børresen-Dale, Anne Lise; Lingjærde, Ole Christian

doi:10.1186/1471-2164-13-591

Cited by 272 publications

(267 citation statements)

References 36 publications

(39 reference statements)

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“…The Battenberg pipeline has high sensitivity for samples with low cellularity, frequently observed in pancreatic tumors. Briefly, the tool phases heterozygous SNPs with use of the 1000 genomes genotypes as a reference panel using Impute2 (17), and corrects phasing errors in regions with copy number changes through segmentation (18). After segmentation of the resulting B-allele frequency (BAF) values, t tests are performed on the BAFs of each copy number segment to identify whether they correspond to the value resulting from a fully clonal copy number change.…”

Section: Discussionmentioning

confidence: 99%

The Genomic Landscape of Pancreatic and Periampullary Adenocarcinoma

et al. 2016

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Despite advances in diagnostics, less than 5% of patients with periampullary tumors experience an overall survival of five years or more. Periampullary tumors are neoplasms that arise in the vicinity of the ampulla of Vater, an enlargement of liver and pancreas ducts where they join and enter the small intestine. In this study, we analyzed copy number aberrations using Affymetrix SNP 6.0 arrays in 60 periampullary adenocarcinomas from Oslo University Hospital to identify genome-wide copy number aberrations, putative driver genes, deregulated pathways, and potential prognostic markers. Results were validated in a separate cohort derived from The Cancer Genome Atlas Consortium (n ¼ 127). In contrast to many other solid tumors, periampullary adenocarcinomas exhibited more frequent genomic deletions than gains. Genes in the frequently codeleted region 17p13 and 18q21/22 were associated with cell cycle, apoptosis, and p53 and Wnt signaling. By integrating genomics and transcriptomics data from the same patients, we identified CCNE1 and ERBB2 as candidate driver genes. Morphologic subtypes of periampullary adenocarcinomas (i.e., pancreatobiliary or intestinal) harbor many common genomic aberrations. However, gain of 13q and 3q, and deletions of 5q were found specific to the intestinal subtype. Our study also implicated the use of the PAM50 classifier in identifying a subgroup of patients with a high proliferation rate, which had impaired survival. Furthermore, gain of 18p11 (18p11. 21-23, 18p11.31-32) and 19q13 (19q13.2, 19q13.31-32) and subsequent overexpression of the genes in these loci were associated with impaired survival. Our work identifies potential prognostic markers for periampullary tumors, the genetic characterization of which has lagged.

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Section: Discussionmentioning

confidence: 99%

The Genomic Landscape of Pancreatic and Periampullary Adenocarcinoma

et al. 2016

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“…Briefly, Battenberg employs Impute2 [42] with the 1000 Genomes haplotypes as a reference panel to phase heterozygous SNPs [43]. Phased SNP B-allele frequency (BAF) values are then segmented using piecewise constant fitting (PCF) [44], resulting in segmented BAF values for each segment. Each identified chromosomal segment is then checked for deviations from clonality using a standard t-test comparing the fitted BAF value to that of a clonal solution.…”

Section: Copy Number Analysis Of Primary Tumorsmentioning

confidence: 99%

Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing

Demeulemeester¹,

Møller²,

Kumar³

et al. 2016

European Journal of Cancer

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Background: Single-cell micro-metastases of solid tumors often occur in the bone marrow. These disseminated tumor cells (DTCs) may resist therapy and lay dormant or progress to cause overt bone and visceral metastases. The molecular nature of DTCs remains elusive, as well as when and from where in the tumor they originate. Here, we apply single-cell sequencing to identify and trace the origin of DTCs in breast cancer.

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“…Raw log2-ratio (logR) calls were adjusted for GC content and quantile normalized. Outliers were detected and modified using Median Absolute Deviation Winsorization prior to patient-specific joint segmentation (gamma = 1,000) [58], to identify genomic segments of constant logR.…”

Section: Copy Number Analysismentioning

confidence: 99%

Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution

et al. 2014

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Background: Genomic analysis of multi-focal renal cell carcinomas from an individual with a germline VHL mutation offers a unique opportunity to study tumor evolution. Results: We perform whole exome sequencing on four clear cell renal cell carcinomas removed from both kidneys of a patient with a germline VHL mutation. We report that tumors arising in this context are clonally independent and harbour distinct secondary events exemplified by loss of chromosome 3p, despite an identical genetic background and tissue microenvironment. We propose that divergent mutational and copy number anomalies are contingent upon the nature of 3p loss of heterozygosity occurring early in tumorigenesis. However, despite distinct 3p events, genomic, proteomic and immunohistochemical analyses reveal evidence for convergence upon the PI3K-AKT-mTOR signaling pathway. Four germline tumors in this young patient, and in a second, older patient with VHL syndrome demonstrate minimal intra-tumor heterogeneity and mutational burden, and evaluable tumors appear to follow a linear evolutionary route, compared to tumors from patients with sporadic clear cell renal cell carcinoma.

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Copynumber: Efficient algorithms for single- and multi-track copy number segmentation

Cited by 272 publications

References 36 publications

The Genomic Landscape of Pancreatic and Periampullary Adenocarcinoma

The Genomic Landscape of Pancreatic and Periampullary Adenocarcinoma

Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing

Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution

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