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Chinese scientists have for the first time identified a hot spot for HPV gene integration

Inputtime:2015-02-03 14:38:00 Views:
Cervical cancer is the most common gynecological malignancy, and human papillomavirus (HPV) infection is considered a major risk factor for cervical cancer, more than 90 percent of cervical cancer is known to be accompanied by HPV infection.
There are many types of HPV, most of which are found and cleared by the body's immune system in the early stages of infection. Only a few (high-risk types) can evade the immune system and remain in the body for decades, leading to cancer.
There are many factors leading to cervical cancer, among which the integration of HPV DNA with host DNA is considered to be the biggest inducing factor of cervical cancer.
This time, from tongji medical college, huazhong university of science and technology, southern medical university and scientific research institutes such as shenzhen bgi team adopts the method of whole genome sequencing of combining self-developed viruses integrate high-throughput screening technology (HIVID) of HPV gene loci and its potential integration mechanisms are discussed in this paper, they not only recalculate the previously reported some popular gene locus of HPV integration frequency, found some new gene integration sites, and the gene of HPV integration mechanism to give answer for the first time.
Their research, published online in the journal Nature Genetics on Jan. 13, 2015, will lead to new methods of diagnosing and screening for cervical cancer.
 
For the study, researchers sampled 135 patients, including 26 with cervical intraepithelial neoplasia, 104 with cervical cancer, and 5 with HPV.
Analyzing the samples, the researchers identified 3,667 integration sites for HPV, including some that had been previously reported.
In all of these samples, the HPV gene integration rate was 76.3%, and the researchers observed that the HPV integration rate increased significantly with the degree of cervical cancer, as shown by the significantly higher integration rate of cervical cancer samples than that of the cervical intraepithelial neoplasia samples.
The researchers then further studied the distribution of integration sites. They recalculated the HPV integration frequency of some previously reported popular integration sites and found that POU5F1B had an integration frequency of 9.7%, FHIT 8.7%, KLF12 7.8%, KLF5 6.8%, LRP1B 5.8% and LEPREL1 4.9%.
More importantly, they also found a number of entirely new integrational sites, HMGA2, with an integration frequency of 7.8%, DLG2 4.9%, and SEMA3D 4.9%.
As HPV integrates, these target genes will be activated or inactivated.
Therefore, the researchers speculate that HPV will effectively examine the entire human genome and then activate or inactivate related genes through its own integration to create more chances to cause the host to become cancerous.
Scientific research on the genetic integration mechanism of HPV has been inconclusive.
This time, the researchers looked at the problem.
They found that homologous tiny pieces of DNA concentrated in and around the integration sites of the human genome and the HPV genome.
Researchers carried on the thorough analysis to this phenomenon and put forward a new integrated model for the virus, that is, in special cases, such as HPV infection, will lead to local genomic fragment unstable and prone to rupture or mismatch, so this will activate the human body in the tiny DNA mediated by homologous DNA repair mechanisms.
And that's when the DNA of HPV sees the opportunity to get ahead of these tiny pieces of homologous DNA and fuse its DNA into the fractured host genome to complete the integration process.
"HPV is small, but it is very harmful," said li weiyang, the project leader from bgi.
In view of the danger of HPV virus and the role of integration in its carcinogenic events, we developed a set of efficient and sensitive methods to detect integration (HIVID).
This study leads us to have an in-depth understanding of the damage and impact of HPV on all aspects at the level of viral integration.
It's not just HPV, there are many integrated viruses that are associated with human disease.
It is believed that the publication of this paper will attract more researchers to focus on the integration of various viruses, so as to solve more scientific and clinical problems.
 
 
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Zheng Hu, Da Zhu, Wei Wang, Weiyang Li, Wenlong Jia, Xi Zeng, Wencheng Ding, Lan Yu, Xiaoli Wang, Liming Wang, Hui Shen, Changlin Zhang, Hongjie Liu, Xiao Liu, Yi Zhao, Xiaodong Fang, Shuaicheng Li,
Wei Chen, Tang Tang, Aisi Fu, Zou Wang, Gang Chen, Qinglei Gao, Shuang Li, Ling Xi, Changyu Wang, Shujie Liao, Xiangyi Ma, Peng Wu, Kezhen Li, Shixuan Wang, Jianfeng Zhou, Jun Wang, Xun Xu,
Hui Wang & Ding Ma. The Genome - wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology - mediated integration mechanism. The Nature Genetics,
12 January 2015;
Doi :10.1038/ng.3178 (news source: biology 360)