Somatic mutations in noncoding sequences are poorly explored in cancer, a rare exception being the recent identification of activating mutations in TERT regulatory DNA. Although this finding is suggestive of a general mechanism for oncogene activation, this hypothesis remains untested. Here we map somatic mutations in 505 tumor genomes across 14 cancer types and systematically screen for associations between mutations in regulatory regions and RNA-level changes. We identify recurrent promoter mutations in several genes but find that TERT mutations are exceptional in showing a strong and genome-wide significant association with increased expression. Detailed analysis of TERT across cancers shows that the strength of this association is highly variable and is strongest in copy number-stable cancers such as thyroid carcinoma. We additionally propose that TERT promoter mutations control expression of the nearby gene CLPTM1L. Our analysis provides a detailed pan-cancer view of TERT transcriptional activation but finds no clear evidence for frequent oncogenic promoter mutations beyond TERT.
A novel gene, CRR9, which was up-regulated in CDDP-resistant ovarian tumor cell line, was associated with apoptosis
Identification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2
Gene trap mutagenesis-based forward genetic approach reveals that the tumor suppressor OVCA1 is a component of the biosynthetic pathway of diphthamide on elongation factor 2.
Mutually exclusive NRASQ61R and BRAFV600E mutations at the single-cell level in the same human melanoma
Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data
OVCA1 inhibits the proliferation of epithelial ovarian cancer cells by decreasing cyclin D1 and increasing p16
A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data
TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal
Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression
Telomerase reverse transcriptase promoter mutations in bladder cancer: high frequency across stages, detection in urine, and lack of association with outcome
Comprehensive mutation analysis of the TERT promoter in bladder cancer and detection of mutations in voided urine
TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism
Telomerase reverse transcriptase gene promoter mutations help discern the origin of urogenital tumors: a genomic and molecular study
Comprehensive analysis of long non-coding RNAs in ovarian cancer reveals global patterns and targeted DNA amplification
A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia
Frequent somatic mutations of the telomerase reverse transcriptase promoter in ovarian clear cell carcinoma but not in other major types of gynaecological malignancy
The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma
An interaction proteomics survey of transcription factor binding at recurrent TERT promoter mutations
Immunoprevalence and magnitude of HLA-DP4 versus HLA-DR-restricted spontaneous CD4(+) Th1 responses against telomerase in cancer patients
Identification of significantly mutated regions across cancer types highlights a rich landscape of functional molecular alterations
Mutation-induced protein interaction kinetics changes affect apoptotic network dynamic properties and facilitate oncogenesis
Association of Telomerase Reverse Transcriptase Promoter Mutations with the Prognosis of Glioma Patients: a Meta-Analysis
A survey of tandem repeat instabilities and associated gene expression changes in 35 colorectal cancers
An APOBEC3A hypermutation signature is distinguishable from the signature of background mutagenesis by APOBEC3B in human cancers
Systematic analysis of somatic mutations driving cancer: uncovering functional protein regions in disease development
Individualized network-based drug repositioning infrastructure for precision oncology in the panomics era
OncodriveFML: a general framework to identify coding and non-coding regions with cancer driver mutations
Identification of High-Impact cis-Regulatory Mutations Using Transcription Factor Specific Random Forest Models
A study of the mutational landscape of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma
Molecular characterisation of cutaneous melanoma: creating a framework for targeted and immune therapies
TERT promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas
A Significant Regulatory Mutation Burden at a High-Affinity Position of the CTCF Motif in Gastrointestinal Cancers
ENDOCRINE TUMOURS: Advances in the molecular pathogenesis of thyroid cancer: lessons from the cancer genome
The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts
Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking
Distribution bias analysis of germline and somatic single-nucleotide variations that impact protein functional site and neighboring amino acids
Identification of novel candidate drivers connecting different dysfunctional levels for lung adenocarcinoma using protein-protein interactions and a shortest path approach
Recurrent promoter mutations in melanoma are defined by an extended context-specific mutational signature
Non-coding cancer driver candidates identified with a sample- and position-specific model of the somatic mutation rate
Identifying mutual exclusivity across cancer genomes: computational approaches to discover genetic interaction and reveal tumor vulnerability
Transcriptome analysis of papillary thyroid cancer harboring telomerase reverse transcriptase promoter mutation
Elevated pyrimidine dimer formation at distinct genomic bases underlies promoter mutation hotspots in UV-exposed cancers
Recurrent Noncoding Mutations in Skin Cancers: UV Damage Susceptibility or Repair Inhibition as Primary Driver?
Pan-cancer screen for mutations in non-coding elements with conservation and cancer specificity reveals correlations with expression and survival
Intragenomic variability and extended sequence patterns in the mutational signature of ultraviolet light
Combining molecular and immunohistochemical analyses of key drivers in primary melanomas: interplay between germline and somatic variations
Clustered somatic mutations are frequent in transcription factor binding motifs within proximal promoter regions in melanoma and other cutaneous malignancies
ncdDetect2: improved models of the site-specific mutation rate in cancer and driver detection with robust significance evaluation
Genome-wide analysis of gynecologic cancer: The Cancer Genome Atlas in ovarian and endometrial cancer
Mutational Signatures Are Critical for Proper Estimation of Purifying Selection Pressures in Cancer Somatic Mutation Data When Using the dN/dS Metric
Recurrent mutations at estrogen receptor binding sites alter chromatin topology and distal gene expression in breast cancer
Advances in computational approaches for prioritizing driver mutations and significantly mutated genes in cancer genomes
Cancer-associated noncoding mutations affect RNA G-quadruplex-mediated regulation of gene expression
ETS transcription factors induce a unique UV damage signature that drives recurrent mutagenesis in melanoma.
Global analysis of somatic structural genomic alterations and their impact on gene expression in diverse human cancers
Mutational signatures of redox stress in yeast single-strand DNA and of aging in human mitochondrial DNA share a common feature
Integrative Analysis of Somatic Mutations in Non-coding Regions Altering RNA Secondary Structures in Cancer Genomes
Scarcity of Recurrent Regulatory Driver Mutations in Colorectal Cancer Revealed by Targeted Deep Sequencing
Mismatch repair-signature mutations activate gene enhancers across human colorectal cancer epigenomes
Functional assessment of CTCF sites at cytokine-sensing mammary enhancers using CRISPR/Cas9 gene editing in mice
Systematic evaluation of the effects of genetic variants on PIWI-interacting RNA expression across 33 cancer types.
Systematic Screening of Promoter Regions Pinpoints Functional Cis-Regulatory Mutations in a Cutaneous Melanoma Genome
Metastatic Melanoma Patient-Derived Xenografts Respond to MDM2 Inhibition as a Single Agent or in Combination with BRAF/MEK Inhibition.
Prediction of survival rate and effect of drugs on cancer patients with somatic mutations of genes: An AI-based approach.
Untangling a complex web: Computational analyses of tumor molecular profiles to decode driver mechanisms.
Differential Allele-Specific Expression Uncovers Breast Cancer Genes Dysregulated by Cis Noncoding Mutations
Candidate Cancer Driver Mutations in Distal Regulatory Elements and Long-Range Chromatin Interaction Networks
Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.
Alzheimer's Disease: MS4A
Variants within the membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease in genome-wide association studies. Here is the latest research on Alzheimer's disease and MS4A.
Pediculosis pubis is a disease caused by a parasitic insect known as Pthirus pubis, which infests human pubic hair, as well as other areas with hair including eye lashes. Here is the latest research.
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Genetic Screens in iPSC-derived Brain Cells
Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells. It also follows CRISPR-Cas9 approaches to generating genetic mutants as a means of understanding the effect of genetics on phenotype.
This feed focuses on molecular models of enzyme evolution and new approaches (such as adaptive laboratory evolution) to metabolic engineering of microorganisms. Here is the latest research.
Chronic Fatigue Syndrome
Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.
Pharmacology of Proteinopathies
This feed focuses on the pharmacology of proteinopathies - diseases in which proteins abnormally aggregate (i.e. Alzheimer’s, Parkinson’s, etc.). Discover the latest research in this field with this feed.
Alignment-free Sequence Analysis Tools
Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.