Role of the Common Fragile Sites in Cancers with a Human Papillomavirus Etiology

Gao, Ge; Smith, Jeremy C.

doi:10.1159/000455287

Cited by 6 publications

(10 citation statements)

References 77 publications

(65 reference statements)

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“…With the development of detection technology, new high-frequency integration sites are constantly found. Existing studies have reported that some Common Fragile Sites (CFS) widely exist in human chromosomes [18], which are often the common integration sites of various carcinogenic virus genes into the human genome including HPV. The reported CFS were 40, and two high-frequency integration sites in the study belong to CFS, such as CSMD1 and CDH13.…”

Section: Discussionmentioning

confidence: 99%

“…(1) Chip Design and Order. We designed the sequencecapture probes according to 20 types of HPV genome (6,11,16,18,31,33,35,39,42,43,44,45,51,52,53,56,58,59, 66, and 68) sequences, and these probes were produced by Agilent Inc., USA. The enrichment chip was also ordered from Agilent Inc., USA.…”

Section: Methodsmentioning

confidence: 99%

“…Comparison of HPV type infection results by highthroughput viral integration detection (HIVID) and flow-through hybridization and gene chip (FHGC). ,11,13,15,18,19,21, and 22, especially in chromosome 19, which had 611 observation integrated events, it is 2.34 times than 261 expectation events.…”

mentioning

confidence: 92%

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Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women

Feng

Sen-Yu

Yuan

et al. 2020

Journal of Immunology Research

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Background. The Uygur is the fifth most populous ethnic group in China. Compared to other Chinese population, cervical cancer in them had high incidence, and HPV infection also was particular. Their HPV integration situation has never been reported. We aimed to investigate the integration situation of 20 subtypes of HPV gene into host cell genome in Chinese Uygur cervical cancer patients; meanwhile, we explored the influence of gene integration on PD-L1 expression. Methods. 40 frozen Chinese Uygur cervical cancer specimens with positive HPV infection were obtained from the cancer prevention and treatment institute of Tumor Hospital Affiliated to Xinjiang Medical University. The integration situation of HPV gene into host cell genome was detected by Agilent SureSelect™ Target Enrichment Chip and Next-Generation Sequencing. The related genes were analyzed by GO functional annotation and KEGG pathway enrichment. The expression levels of PD-L1 in cancer cells were tested by immunohistochemical assay (IHC). Meanwhile, the relationship between PD-L1 levels in cancer cells and gene integration were analyzed. Results. The HPV multiple infection rate by HIVID was as high as 92.5%, much higher than 35.0% by the commercial kit (P<0.05). There were 13423 integration events in 40 specimens, involving 6867 human genes. These integration events were distributed on all human chromosomes, and chromosome 19 had the excessive concentration phenomenon of integration events. There were some integration hotspots in human genome such as PPP1R37, HECW2, EMBP1, ANKRD50, SPTBN4, LINC00895, LYRM4-AS1, LINC00374, RBFOX1, CSMD1, CDH13, and KLHL4. Insertion breakpoints can be found in all gene regions of the HPV genome. The actual observation of the integration times of E1 and E6 was much higher than the expected value, while the actual observation times of E5 were much lower than the expected value. The result of GO functional analysis showed that binding molecular function and cellular process biological process were the main ways to influence the cell biological behavior of HPV gene integration. The enrichment pathway analysis of KEGG showed that pathways in cancer were the most important enrichment pathways involved in the genomic integration of HPV. The positive PD-L1 rate was 62.5%. Logistic regression analysis showed that 9p24.1 existing integration sites and the number of all gene integration were risk factors for PD-L1 expression (odds ratio 17.313 and 1.012; 95% confidence interval 1.691-177.213 and 1.001-1.023). Conclusions and Relevance. Most high-frequency sites of HPV integration in Chinese Uygur cervical cancer are related to cancer progression, and the gene integration hotspots may be potential HPV carcinogenic targets. The problem of multiple HPV infection in Chinese Uygur cervical cancer patients should be paid attention. L1 and E6 genes are inapposite as the target gene of commercial HPV type detection kit, because of high-frequency breakpoints in these genes. The gene integration especially the integration existing on 9p24.1 could affect the expression level of PD-L1.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women

Feng

Sen-Yu

Yuan

et al. 2020

Journal of Immunology Research

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“…In regards to eukaroytes, some patterns in genome size have been discussed ( Lynch and Conery 2003 ; Daubin and Moran 2004 ; Lynch 2004 ). Additionally, a handful of studies have analyzed genome size in connection to other parameters such as indels ( Pettersson et al 2009 ), transposon content ( Kidwell 2002 ; Elliott and Gregory 2015a ; Canapa et al 2016 ), average intron length ( Deutsch and Long 1999 ; Zhu et al 2009 ) or total intron length ( Elliott and Gregory 2015b ). Despite these advances, none of these studies have estimated the amount of the genome that is genic (exonic plus intronic, including noncoding) based on independent examination of single genomes and without averaging over a whole kingdom.…”

Section: Introductionmentioning

confidence: 99%

Similar Ratios of Introns to Intergenic Sequence across Animal Genomes

Francis

Wörheide

2017

Genome Biology and Evolution

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One central goal of genome biology is to understand how the usage of the genome differs between organisms. Our knowledge of genome composition, needed for downstream inferences, is critically dependent on gene annotations, yet problems associated with gene annotation and assembly errors are usually ignored in comparative genomics. Here, we analyze the genomes of 68 species across 12 animal phyla and some single-cell eukaryotes for general trends in genome composition and transcription, taking into account problems of gene annotation. We show that, regardless of genome size, the ratio of introns to intergenic sequence is comparable across essentially all animals, with nearly all deviations dominated by increased intergenic sequence. Genomes of model organisms have ratios much closer to 1:1, suggesting that the majority of published genomes of nonmodel organisms are underannotated and consequently omit substantial numbers of genes, with likely negative impact on evolutionary interpretations. Finally, our results also indicate that most animals transcribe half or more of their genomes arguing against differences in genome usage between animal groups, and also suggesting that the transcribed portion is more dependent on genome size than previously thought.

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“…Besides cervical cancer, HPV infection has also been etiologically associated and implicated with the development of other anogenital cancers (vulva, vagina, anus and penis) [58,59,60]. An estimated 85% of anal cancers and approximately a half of the vulvar, vaginal and penile cancers are attributable to HPV [61,62]. However, apart from the many studies that associated HPV with anogenital cancers, little is known about how HPV actually contributes to the development of these cancers [61].…”

Section: Other Anogenital Cancersmentioning

confidence: 99%

The Role of MicroRNAs in the Metastatic Process of High-Risk HPV-Induced Cancers

Santos

Silva

Costa

et al. 2018

Cancers

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High-risk human papillomavirus (HPV)-driven cancers represent a major health concern worldwide. Despite the constant effort to develop and promote vaccination against HPVs, there is still a high percentage of non-vaccinated population. Furthermore, secondary prevention programs are not ubiquitous worldwide and not widely followed. Metastatic disease is the cause of the great majority of cancer-associated deaths, making it essential to determine its underlying mechanisms and to identify actionable anti-metastatic targets. Within certain types of cancer (e.g., head and neck), HPV-positive tumors show different dissemination patterns when compared with their HPV-negative counterparts, implicating HPV-related factors in the metastatic process. Among the many groups of biomolecules dysregulated by HPV, microRNAs have recently emerged as key regulators of carcinogenesis, able to control complex processes like cancer metastization. In this review, we present recent data on the role of microRNAs in the metastization of HPV-related cancers and on their possible clinical relevance as biomarkers of metastatic disease and/or as therapeutic targets.

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Role of the Common Fragile Sites in Cancers with a Human Papillomavirus Etiology

Cited by 6 publications

References 77 publications

Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women

Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women

Similar Ratios of Introns to Intergenic Sequence across Animal Genomes

The Role of MicroRNAs in the Metastatic Process of High-Risk HPV-Induced Cancers

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