Deregulation of <scp>SYCP</scp>2 predicts early stage human papillomavirus‐positive oropharyngeal carcinoma: A prospective whole transcriptome analysis

Masterson, Liam; Sorgeloos, Frédéric; Winder, David M.; Lechner, Matt; Marker, Alison; Malhotra, Shalini; Sudhoff, Holger; Jani, Piyush; Goon, Peter; Sterling, Jane

doi:10.1111/cas.12809

Cited by 98 publications

(112 citation statements)

References 45 publications

(107 reference statements)

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“…Actually, c - MYC is typically amplified in HPV16 cervical squamous cell carcinomas [25, 26], and its binding to the consensus DNA element is reported to be methylation-sensitive, in particular at CpG islands and nearby regions, supporting our finding of an interaction at hypomethylated regions at CpG island shores [27, 28]. …”

Section: Resultssupporting

confidence: 80%

“…3). In fact, a recent study describes that SYCP2 up-regulation predicts early stage HPV(16) oropharyngeal carcinomas [28]. Moreover, we identified a minimal epigenetic signature made of five CpGs encompassing three genetic loci (B3GALT6-SDF4, SYCP2-FAM127B and HTLF-HLTF-AS1) that showed a high specificity (>95%) in identifying HPV(+) cases, independent of the anatomic site.…”

Section: Discussionmentioning

confidence: 72%

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Unique DNA methylation signature in HPV-positive head and neck squamous cell carcinomas

et al. 2017

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BackgroundHead and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of cancers for which human papilloma virus (HPV) infection is an emerging risk factor. Previous studies showed promoter hypermethylation in HPV(+) oropharyngeal cancers, but only few consistent target genes have been so far described, and the evidence of a functional impact on gene expression is still limited.MethodsWe performed global and stratified pooled analyses of epigenome-wide data in HNSCCs based on the Illumina HumanMethylation450 bead-array data in order to identify tissue-specific components and common viral epigenetic targets in HPV-associated tumours.ResultsWe identified novel differentially methylated CpGs and regions associated with viral infection that are independent of the anatomic site. In particular, most hypomethylated regions were characterized by a marked loss of CpG island boundaries, which showed significant correlations with expression of neighbouring genes. Moreover, a subset of only five CpGs in a few hypomethylated regions predicted HPV status with a high level of specificity in different cohorts. Finally, this signature was a better predictor of survival compared with HPV status determined by viral gene expression by RNA sequencing in The Cancer Genome Atlas cohort.ConclusionsWe identified a novel epigenetic signature of HPV infection in HNSCCs which is independent of the anatomic site, is functionally correlated with gene expression and may be leveraged for improved stratification of prognosis in HNSCCs.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0419-z) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 80%

Section: Discussionmentioning

confidence: 72%

Unique DNA methylation signature in HPV-positive head and neck squamous cell carcinomas

et al. 2017

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“…6C). Hi-C and ChIA-PET linkages indicated that the region is within a TAD and validated a regulatory connection to the cancer-associated gene SYCP2 67 . We further observed strong binding of many TFs in this region in MCF-7.…”

Section: The Extended Gene Representationmentioning

confidence: 82%

An integrative ENCODE resource for cancer genomics

Zhang

Lee

Dhiman

et al. 2019

Preprint

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ENCODE comprises thousands of functional genomics datasets, and the encyclopedia covers hundreds of cell types, providing a universal annotation for genome interpretation. However, for particular applications, it may be advantageous to use a customized annotation. Here, we develop such a custom annotation by leveraging advanced assays, such as eCLIP, Hi-C, and whole-genome STARR-seq on a number of data-rich ENCODE cell types. A key aspect of this annotation is comprehensive and experimentally derived networks of both transcription factors and RNAbinding proteins (TFs and RBPs). Cancer, a disease of system-wide dysregulation, is an ideal application for such a network-based annotation. Specifically, for cancer-associated cell types, we put regulators into hierarchies and measure their network change (rewiring) during oncogenesis. We also extensively survey TF-RBP crosstalk, highlighting how SUB1, a previously uncharacterized RBP, drives aberrant tumor expression and amplifies the effect of MYC, a wellknown oncogenic TF. Furthermore, we show how our annotation allows us to place oncogenic transformations in the context of a broad cell space; here, many normal-to-tumor transitions move towards a stem-like state, while oncogene knockdowns show an opposing trend. Finally, we organize the resource into a coherent workflow to prioritize key elements and variants, in addition to regulators. We showcase the application of this prioritization to somatic burdening, cancer differential expression and GWAS. Targeted validations of the prioritized regulators, elements and variants using siRNA knockdowns, CRISPR-based editing, and luciferase assays demonstrate the value of the ENCODE resource.

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“…Linkage to oesophageal cancer (Wu, Song, Pang, & Chen, ) and oropharyngeal squamous cell carcinomas (Masterson et al., )…”

Section: Discussionmentioning

confidence: 99%

“…The identification of saliva-derived mRNA in normal and cancer patients (Hu et al, 2008;Li et al, 2004) and other forensic applications (Juusola & Ballantyne, 2005) (Gibbs et al, 1993;Stemmler et al, 2009) Assessment of the regenerative potential of injured neurons (Starkey et al, 2009) m2 lnc-TET3-2:1 NONHSAT071649 A member of the ten-eleven translocation (TET) gene family, that plays a role in the DNA methylation process (Langemeijer et al, 2009) (Ragvin et al, 2010) Airway inflammation (Kuwahara et al, 2012) m7 FAM25A NM_001146157 Inflammation and infectious disease, decrease in immune response (Deloukas et al, 2004;Mauritz et al, 2010;Wang et al, 2014) m10 CRCT1 NM_019060 Linkage to oesophageal cancer (Wu, Song, Pang, & Chen, 2016) and oropharyngeal squamous cell carcinomas (Masterson et al, 2015) Early Alzheimer's disease-related stages (Parra-Damas et al, 2014) Promotion of tumour cell apoptosis and upregulation of the expression of apoptosis-related proteins (Wu et al, 2016) TA B L E 3 Description of functions and biological roles of validated exRNAs for gingivitis neutrophil, eosinophil and macrophage chemotaxis, etc.) and biological functions (antimicrobial activity, etc.)…”

Section: Discussionmentioning

confidence: 99%