Dataset Information

The characteristics of HPV integration in cervical intraepithelial cells.

ABSTRACT: Cervical cancer is one of the most common malignant tumors in gynecology. Deploying HIVID, a cost-effective technique to detect HPV integration sites, our team had studied the characteristics of HPV integrations in cervical exfoliated cells. Our results indicated that both the sample proportion and the number of HPV integrations gradually increased following the development of cervical lesion. Meanwhile, our data also revealed that there were recurrent genes integrated by HPV in cervical exfoliated cells. Collectively, the HPV integration breakpoints were highly enriched in the intron and promoter regions. Intriguingly, the gene pathway analysis indicated that the HPV-integrated genes were strongly inclined to pathways of metabolism of xenobiotics by cytochrome P450, chemical carcinogenesis and steroid hormone biosynthesis. In conclusion, this study unveiled the HPV integration patterns and the associated recurrent genes in cervical epithelial exfoliated cells. Altogether, our data suggested that the HPV integrations in cervical exfoliated cells might have vital clinical significance, and probably also diagnostic and/or prognostic values in future clinical applications.

SUBMITTER: Li W

PROVIDER: S-EPMC6584928 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The characteristics of HPV integration in cervical intraepithelial cells.

Li Weiping W Tian Shuang S Wang Pengpeng P Zang Yikun Y Chen Xin X Yao Yuanqing Y Li Weiyang W

Journal of Cancer 20190602 12

Cervical cancer is one of the most common malignant tumors in gynecology. Deploying HIVID, a cost-effective technique to detect HPV integration sites, our team had studied the characteristics of HPV integrations in cervical exfoliated cells. Our results indicated that both the sample proportion and the number of HPV integrations gradually increased following the development of cervical lesion. Meanwhile, our data also revealed that there were recurrent genes integrated by HPV in cervical exfolia ...[more]

PMID: 31258786

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Project description:BACKGROUND: The development of cervical cancer and its high-grade precursor lesions (Cervical Intraepithelial Neoplasia grade 2/3 [CIN2/3]) result from a persistent infection with high-risk human papillomavirus (hrHPV) types and the accumulation of (epi)genetic host cell aberrations. Epidemiological studies have demonstrated variable CIN2/3 and cancer risks between different hrHPV types. Recent genomic profiling studies revealed substantial heterogeneity in the chromosomal aberrations detected in morphologically indistinguishable CIN2/3 suggestive of varying cancer risk. The current study aimed to investigate whether CIN2/3 with different hrHPV types vary with respect to their chromosomal profiles, both in terms of the number of aberrations and chromosomal loci affected. METHODS: Chromosomal profiles were determined of 43 p16INK4a-immunopositive CIN2/3 of women with long-term hrHPV infection (? 5 years). Sixteen lesions harboured HPV16, 3 HPV18, 14 HPV31, 1 HPV33, 4 HPV45, 1 HPV51, 2 HPV52 and 2 HPV58. RESULTS: Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two major clusters, characterised by either few or multiple chromosomal aberrations, respectively. A majority of 87.5% of lesions with HPV16 were in the cluster with relatively few aberrations, whereas no such unbalanced distribution was seen for lesions harbouring other hrHPV types. Analysis of the two most prevalent types (HPV16 and HPV31) in this data set revealed a three-fold increase in the number of losses in lesions with HPV31 compared to HPV16-positive lesions. In particular, losses at chromosomes 2q, 4p, 4q, 6p, 6q, 8q & 17p and gain at 1p & 1q were significantly more frequent in HPV31-positive lesions (FDR < 0.2). CONCLUSIONS: Chromosomal aberrations in CIN2/3 are at least in part related to the hrHPV type present. The relatively low number of chromosomal aberrations observed in HPV16-positive CIN2/3 suggests that the development of these lesions is less dependent on genetic insult than those caused by other types like HPV31.

Dataset Information

The characteristics of HPV integration in cervical intraepithelial cells.

Publications

The characteristics of HPV integration in cervical intraepithelial cells.

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