GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers

Mermel, Craig H.; Schumacher, Steven E.; Hill, Barbara; Meyerson, Matthew; Beroukhim, Rameen; Getz, Gad

doi:10.1186/gb-2011-12-4-r41

Cited by 2,831 publications

(2,610 citation statements)

References 43 publications

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“…Next, the GISTIC 2.0 was used to determine the significantly copy number amplifications and deletions of recurrent lncRNAs genomic regions 22. Then, each of the lncRNAs genomic regions was mapped to the GISTIC peaks.…”

Section: Methodsmentioning

confidence: 99%

Identification of differential expressed lncRNAs in human thyroid cancer by a genome‐wide analyses

et al. 2018

Cancer Medicine

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Recently, a growing number of evidence has revealed that long noncoding RNAs (lncRNAs) act as key regulators in various cellular biologic processes, and dysregulation of lncRNAs involves in tumorigenesis and cancer progression. However, the expression pattern, clinical relevance, and biologic function of most lncRNAs in human thyroid cancer remain unclear. To identify more thyroid‐cancer‐associated lncRNAs, we analyzed the expression profile of lncRNAs in thyroid cancer tissues and adjacent normal or non‐tumor tissues using RNA sequencing data and gene microarray data from The Cancer Genome Atlas and Gene Expression Omnibus. Annotation and analyses of these data revealed that hundreds of lncRNAs are differentially expressed in thyroid cancer tissues when compared with normal tissues. By copy number variation analyses, we identified that some of those dysregulated lncRNAs genome locus are accompanied with the copy number amplification or deletion. Moreover, some lncRNAs expression levels are significantly associated with thyroid cancer patients overall or recurrence‐free survival time, such as RUNDC3A‐AS1, FOXD2‐AS1, PAX8‐AS1, and CRYM‐AS1. Furthermore, we validated an lncRNA termed LINC00704 in thyroid cancer cells by performing loss of function assays. Downregulation of LINC00704 could significantly impair thyroid cancer cells proliferation, colony formation, inhibit cell‐cycle progression and cell invasion, and induce cell apoptosis. Taken together, our findings reveal that lots of lncRNAs are dysregulated and may play critical roles in thyroid cancer, and this study could provide useful resource for identification and investigation of novel lncRNA candidates for thyroid cancer.

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Section: Methodsmentioning

confidence: 99%

Identification of differential expressed lncRNAs in human thyroid cancer by a genome‐wide analyses

et al. 2018

Cancer Medicine

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“…We analyzed TCGA samples with available copy-number variation (CNV) data using the GISTIC 2.0 software (Mermel et al 2011). First, we carried out a pan-cancer analysis and found only five core target genes to be lost at a significant rate (FAM212B, ASCC3, PRDM1, SESN1, and PARD6G) ( Fig.…”

Section: Wwwgenomeorgmentioning

confidence: 99%

Identification of a core TP53 transcriptional program with highly distributed tumor suppressive activity

et al. 2017

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The tumor suppressor TP53 is the most frequently mutated gene product in human cancer. Close to half of all solid tumors carry inactivating mutations in the TP53 gene, while in the remaining cases, TP53 activity is abrogated by other oncogenic events, such as hyperactivation of its endogenous repressors MDM2 or MDM4. Despite identification of hundreds of genes regulated by this transcription factor, it remains unclear which direct target genes and downstream pathways are essential for the tumor suppressive function of TP53. We set out to address this problem by generating multiple genomic data sets for three different cancer cell lines, allowing the identification of distinct sets of TP53-regulated genes, from early transcriptional targets through to late targets controlled at the translational level. We found that although TP53 elicits vastly divergent signaling cascades across cell lines, it directly activates a core transcriptional program of ∼100 genes with diverse biological functions, regardless of cell type or cellular response to TP53 activation. This core program is associated with high-occupancy TP53 enhancers, high levels of paused RNA polymerases, and accessible chromatin. Interestingly, two different shRNA screens failed to identify a single TP53 target gene required for the anti-proliferative effects of TP53 during pharmacological activation in vitro. Furthermore, bioinformatics analysis of thousands of cancer genomes revealed that none of these core target genes are frequently inactivated in tumors expressing wild-type TP53. These results support the hypothesis that TP53 activates a genetically robust transcriptional program with highly distributed tumor suppressive functions acting in diverse cellular contexts.

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“…Whole-chromosome arm copy number was determined using an 80% length threshold and a segment mean threshold of AE0.2. Analysis of focal copy-number alterations was performed using the GISTIC 2.0 algorithm (18).…”

Section: Copy-number Variance Analysismentioning

confidence: 99%

Prognostic Impact of Novel Molecular Subtypes of Small Intestinal Neuroendocrine Tumor

Karpathakis

Dibra

Pipinikas

et al. 2016

Clinical Cancer Research

165

149

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Purpose: Small intestinal neuroendocrine tumors (SINET) are the commonest malignancy of the small intestine; however, underlying pathogenic mechanisms remain poorly characterized. Whole-genome and -exome sequencing has demonstrated that SINETs are mutationally quiet, with the most frequent known mutation in the cyclin-dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ∼8% of tumors, suggesting that alternative mechanisms may drive tumorigenesis. The aim of this study is to perform genome-wide molecular profiling of SINETs in order to identify pathogenic drivers based on molecular profiling. This study represents the largest unbiased integrated genomic, epigenomic, and transcriptomic analysis undertaken in this tumor type. Experimental Design: Here, we present data from integrated molecular analysis of SINETs (n = 97), including whole-exome or targeted CDKN1B sequencing (n = 29), HumanMethylation450 BeadChip (Illumina) array profiling (n = 69), methylated DNA immunoprecipitation sequencing (n = 16), copy-number variance analysis (n = 47), and Whole-Genome DASL (Illumina) expression array profiling (n = 43). Results: Based on molecular profiling, SINETs can be classified into three groups, which demonstrate significantly different progression-free survival after resection of primary tumor (not reached at 10 years vs. 56 months vs. 21 months, P = 0.04). Epimutations were found at a recurrence rate of up to 85%, and 21 epigenetically dysregulated genes were identified, including CDX1 (86%), CELSR3 (84%), FBP1 (84%), and GIPR (74%). Conclusions: This is the first comprehensive integrated molecular analysis of SINETs. We have demonstrated that these tumors are highly epigenetically dysregulated. Furthermore, we have identified novel molecular subtypes with significant impact on progression-free survival. Clin Cancer Res; 22(1); 250–8. ©2015 AACR.

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GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers

Cited by 2,831 publications

References 43 publications

Identification of differential expressed lncRNAs in human thyroid cancer by a genome‐wide analyses

Identification of differential expressed lncRNAs in human thyroid cancer by a genome‐wide analyses

Identification of a core TP53 transcriptional program with highly distributed tumor suppressive activity

Prognostic Impact of Novel Molecular Subtypes of Small Intestinal Neuroendocrine Tumor

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