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Intratumoral heterogeneity and clonal evolution induced by HPV integration

ABSTRACT: Intratumoral heterogeneity and clonal evolution induced by HPV integration

PROVIDER: PRJNA1006805 | ENA |

REPOSITORIES: ENA

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Intratumoral heterogeneity and clonal evolution induced by HPV integration

Project description:Intratumoral heterogeneity and clonal evolution induced by HPV integration

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Intratumoral Heterogeneity and Clonal Evolution Induced by HPV Integration.

Project description: Not available

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HPV integration generates cellular super enhancer and functions as ecDNA to regulate genome-wide transcription

Project description:Human papillomavirus (HPV) integration is a critical step in cervical cancer development, while the oncogenic mechanism in genome-wide transcriptional level is still poorly understood. In this study, we employed integrative analysis on multi-omics data of cervical cancer cell lines. Through HPV integration detection, super enhancer (SE) identification, SE-associated gene expression and extrachromosomal DNA (ecDNA) investigation, we aimed to explore the genome-wide transcriptional influence of HPV integration. We identified 5 high-ranking cellular super enhancers generated by HPV integration (the HPV breakpoint induced cellular super enhancers, BP-cSE), leading to intra-chromosomal and inter-chromosomal regulations of chromosomal genes. The pathway analysis showed the dysregulated chromosomal genes were correlated to cervical cancer associated pathways. Importantly, we demonstrated that BP-cSE existed in the HPV-host ecDNA, explaining above transcription alterations. Our results suggest that HPV integration generates cellular super enhancers and functions as ecDNA to regulate unconstraint transcription, expanding the tumorigenic mechanism of HPV integration and providing insights of developing new diagnostic and therapeutic strategies.

2023-04-19 | GSE195631 | GEO

Intratumoral heterogeneity and clonal evolution in liver cancer.

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Genome-wide profiling of HPV integration in cervical intraepithelial neoplasia identifies enrichment of genetic elements associated with carcinogenesis

Project description:To investigate differences in the transcriptome between precancerous lesions with HPV integration and precancerous lesions without HPV integration, 15 CIN3 tissue samples (11 integration-positive and 4 integration-negative samples as identified by high-throughput viral integration detection (HIVID)) were collected for RNA sequencing.

2025-10-15 | GSE189452 | GEO

Intratumoral heterogeneity of prostate cancers

Project description:Copy number analyses of regionally separated intratumoral biopsies of prostate cancers. Intratumoral heterogeneity (ITH) leads to regional biases of the mutational landscape in a single tumor and may influence the single biopsy-based clinical diagnosis and treatment decision. To evaluate the extent of ITH in unifocal prostate cancers (PCAs) that had not been sought, we analyzed multiple regional biopsies from three PCAs using DNA copy number analyses. DNA copy number showed ITH including regional biases in the presentation of a well-known driver of TMPRSS2-ERG fusion. Our analyses identified a substantial level of genetic ITH in unifocal PCAs at the genomic levels, which should be taken into account for the curation of biomarkers in the clinical setting. Four intratumoral biopsies were obtained per tumor for three prostate cancers. Radical prostatectomy tissue from three patients with prostate cancers were obtained. Board-certified pathologists reviewed the hematoxylin&eosin stained sections and identified tumor-rich regions (> 80% purity). We selected four different areas for biopsy that were at least 5mm apart and were comprised of the most common Gleason pattern (the most common histologic patterns with minimal histologic differences). Copy number profiling was performed using Agilent 180K platform according to the manufacturer's protocol.

2014-01-18 | E-GEOD-54185 | biostudies-arrayexpress

HPV genome expression at invasive cervical carcinomas infected by multiple HPV genotypes

Project description:Multiple HPV genotypes infection is frequently detected in HPV+ cervical lesions, however it is not well stablished how is the different viral interaction during the carcinogenic process. Here we carried out a comprehensive study to characterize the multiple HPV genome expression and integration by RNA-Seq analysis in 19 invasive cervical carcinomas with HPV coinfections. Analysis of tumoral DNA by a hybridization kit indicated multi-infection ranging from 2 to 6 different HPV genotypes, without a preferential species coinfection. The expression analysis showed that a single HPV genotype preferentially expressed its genome, might indicating a competition between the infecting virus. Finally, the search for HPV/human chimeric transcripts indicated integration from just one HPV in almost all samples, corroborating the expression findings.

2021-07-28 | GSE144293 | GEO

Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma.

Project description: Not available

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Stable global repertoire architecture masks short- term clonal remodeling in intratumoral TCR repertoires

Project description:Background: Tumor-in ltrating T cell receptor repertoires are increasingly pro led to assess intratumoral T cell dynamics and inform prognosis and treatment response. Most analyzes rely on aggregate diversity metrics, such as Shannon index or clonality, which describe overall repertoire structure but do not resolve changes in clonotype identity over time. Thus, intrinsic temporal dynamics of intratumoral T cell receptor repertoires during tumor progression remain incompletely de ned. Methods: In a bilateral murine cancer model, one tumor was surgically removed, and the paired tumor was collected 11 days later. The T cell receptor repertoires of these tumors, and of synchronously harvested bilateral tumors from separate control animals, were analyzed using diversity metrics, Morisita–Horn similarity, and clonal tracking approaches. Results: Time-matched bilateral tumors exhibited highly similar clonotype composition and abundance. In contrast, time-separated tumors showed reduced clonal overlap, increased fractions of private clonotypes, and redistribution of dominant clones. These changes occurred despite preserved global repertoire metrics, including clonotype number, Shannon diversity, and Gini coef cient. Conclusion: Short-term tumor progression is associated with clear changes in the composition of the intratumoral T cell receptor repertoire, even when overall diversity appears stable. These results suggest that relying solely on global diversity metrics can obscure active clonal remodeling, underscoring the importance of monitoring individual T cell clonotypes to accurately capture intratumoral T cell dynamics over time.

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Intratumoral heterogeneity in cholangiocarcinoma

Project description:Intratumoral heterogeneity in cholangiocarcinoma

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