Genome-wide profiling of the human papillomavirus DNA integration in cervical intraepithelial neoplasia and normal cervical epithelium by HPV capture technology

Liu, Ying; Zhang, Chaoting; Gao, Weiwei; Wang, Limin; Pan, Yaqi; Gao, Yunong; Lu, Zheming; Ke, Yang

doi:10.1038/srep35427

Cited by 32 publications

(44 citation statements)

References 14 publications

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“…Hybridization capture plus massively parallel sequencing has been used and proven to be reliable for identifying human genome integration sites of HPV DNA in tumors. 20,21,24,46 As demonstrated here, this amplification were all likely important genetic components that function together at least to maintain this tumor. Surprisingly, the RNAseq results revealed that only a small fraction of transcripts encompassed the start codon of the E6 ORF, with most initiating further downstream in the E6 ORF.…”

Section: Discussionsupporting

confidence: 54%

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Insertional oncogenesis by HPV70 revealed by multiple genomic analyses in a clinically HPV‐negative cervical cancer

Arsdale

Patterson

Maggi

et al. 2019

Genes Chromosomes & Cancer

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Cervical carcinogenesis, the second leading cause of cancer death in women worldwide, is caused by multiple types of human papillomaviruses (HPVs). To investigate a possible role for HPV in a cervical carcinoma that was HPV‐negative by PCR testing, we performed HPV DNA hybridization capture plus massively parallel sequencing. This detected a subgenomic, URR‐E6‐E7‐E1 segment of HPV70 DNA, a type not generally associated with cervical cancer, inserted in an intron of the B‐cell lymphoma/leukemia 11B (BCL11B) gene in the human genome. Long range DNA sequencing confirmed the virus and flanking BCL11B DNA structures including both insertion junctions. Global transcriptomic analysis detected multiple, alternatively spliced, HPV70‐BCL11B, fusion transcripts with fused open reading frames. The insertion and fusion transcripts were present in an intraepithelial precursor phase of tumorigenesis. These results suggest oncogenicity of HPV70, identify novel BCL11B variants with potential oncogenic implications, and underscore the advantages of thorough genomic analyses to elucidate insights into HPV‐associated tumorigenesis.

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Section: Discussionsupporting

confidence: 54%

“…Hybridization capture plus massively parallel sequencing has been used and proven to be reliable for identifying human genome integration sites of HPV DNA in tumors . As demonstrated here, this approach is best applied by use of capture DNA probes encompassing the complete viral genomes of multiple HPV types.…”

Section: Discussionmentioning

confidence: 99%

Insertional oncogenesis by HPV70 revealed by multiple genomic analyses in a clinically HPV‐negative cervical cancer

Arsdale

Patterson

Maggi

et al. 2019

Genes Chromosomes & Cancer

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“…Our findings suggested that the HPV prevalence in cells did not correspond well to that observed in tissues. It should be noted that the complex link between historical infections and current disease status might be related to HPV genome integration status [ 69 ]. In addition, HPV type-specific primers are usually designed to amplify shorter sequences of HPV DNA and might be more sensitive for detection of HPV DNA sequences.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of human papillomavirus genotypes and relative risk of cervical cancer in China: a systematic review and meta-analysis

Wang

Feng

et al. 2018

Oncotarget

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High-risk HPV (hrHPV) is related to cervical carcinogenesis, although clinical data comparing the natural history and carcinogenic potential of type-specific HPV remain limited. Furthermore, the nationwide prevalence rates of overall and type-specific HPV among women with cervical precancerous lesions and cancer have not been reported. Here, a meta-analysis was performed for type-specific HPV distribution among 30,165 HPV-positive women, including 12,094 invasive cervical cancers (ICCs), 10,026 cervical intraepithelial neoplasia grade 2/3 (CIN2/3), 3246 CIN1, and 4799 normal cervices from 45 PCR-based studies. We found that HPV16 was the most common hrHPV type involved in cervical disease. The HPV16 positivity rate varied little across normal (22.7%) and CIN1 individuals (23.6%) but increased through the CIN2 (37.6%) and CIN3 patients (51.9%) to 65.6% in ICC cases. HPV16, 18, 35, 39, 45, and 59 were more frequent in ICC than CIN3, with ICC:CIN3 ratios ranging from 2.3 for HPV18 to 1.1 for HPV35/45. HPV31, 33, 52, and 58 were more frequent in CIN3 compared with normal cervices but less common in ICC compared with CIN3 (ICC:CIN3 ratios ranging from 0.6 for HPV58 and 0.4 for HPV52). The ICC:normal ratios were particularly high for HPV18, 52 and 58 in West China (4.1, 3.9 and 2.9, respectively) and for HPV45 and 59 in North China (1.6 and 1.1, respectively). In summary, this study is the most comprehensive analysis of type-specific HPV distribution in cervical carcinogenesis and could be valuable for HPV-based cervical cancer screening strategies and vaccination policies in China.

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“…The discovery of new therapeutic interventions for HNSCC requires conducting preclinical studies, which rely heavily on human tumor cell lines. Several reports have identified actionable molecular targets by investigating the genomic characteristics of HNSCC cell lines and tumors [ 11 – 13 ]. Recent mutational and transcriptomic analyses of up to 22 HNSCC cell lines have provided valuable data on the characteristics of HNSCCs [ 11 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Genomic characterization of human papillomavirus-positive and -negative human squamous cell cancer cell lines

et al. 2017

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Human cancer cell lines are the most frequently used preclinical models in the study of cancer biology and the development of therapeutics. Although anatomically diverse, human papillomavirus (HPV)-driven cancers have a common etiology and similar mutations that overlap with but are distinct from those found in HPV-negative cancers. Building on prior studies that have characterized subsets of head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESC) cell lines separately, we performed genomic, viral gene expression, and viral integration analyses on 74 cell lines that include all readily-available HPV-positive (9 HNSCC, 8 CESC) and CESC (8 HPV-positive, 2 HPV-negative) cell lines and 55 HPV-negative HNSCC cell lines. We used over 700 human tumors for comparison. Mutation patterns in the cell lines were similar to those of human tumors. We confirmed HPV viral protein and mRNA expression in the HPV-positive cell lines. We found HPV types in three CESC cell lines that are distinct from those previously reported. We found that cell lines and tumors had similar patterns of viral gene expression; there were few sites of recurrent HPV integration. As seen in tumors, HPV integration did appear to alter host gene expression in cell lines. The HPV-positive cell lines had higher levels of p16 and lower levels of Rb protein expression than did the HPV-negative lines. Although the number of HPV-positive cell lines is limited, our results suggest that these cell lines represent suitable models for studying HNSCC and CESC, both of which are common and lethal.

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Genome-wide profiling of the human papillomavirus DNA integration in cervical intraepithelial neoplasia and normal cervical epithelium by HPV capture technology

Cited by 32 publications

References 14 publications

Insertional oncogenesis by HPV70 revealed by multiple genomic analyses in a clinically HPV‐negative cervical cancer

Insertional oncogenesis by HPV70 revealed by multiple genomic analyses in a clinically HPV‐negative cervical cancer

Prevalence of human papillomavirus genotypes and relative risk of cervical cancer in China: a systematic review and meta-analysis

Genomic characterization of human papillomavirus-positive and -negative human squamous cell cancer cell lines

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