HPV VIS Detail Information

> This page shows VIS [5009791] detail information, including site information (chromosome, GRCh38 location, disease, sample, etc) and literature information.

Site Information

DVID	5009791
Chromosome	chr7
GRCh38 Location	88147743
Disease	Cervical Intraepithelial Neoplasia
Sample	tumor
Target Gene	ADAM22

Literature Information

PubMed PMID	31102403
Year	2019 Oct 16;40(10):1220-1228
Journal	Carcinogenesis
Title	Risk stratification of cervical lesions using capture sequencing and machine learning method based on HPV and human integrated genomic profiles.
Author	Tian R,Cui Z,He D,Tian X,Gao Q,Ma X,Yang JR,Wu J,Das BC,Severinov K,Hitzeroth II,Debata PR,Xu W,Zhong H,Fan W,Chen Y,Jin Z,Cao C,Yu M,Xie W,Huang Z,Bao Y,Xie H,Yao S,Hu Z
Evidence	From initial human papillomavirus (HPV) infection and precursor stages, the development of cervical cancer takes decades. High-sensitivity HPV DNA testing is currently recommended as primary screening method for cervical cancer, whereas better triage methodologies are encouraged to provide accurate risk management for HPV-positive women. Given that virus-driven genomic variation accumulates during cervical carcinogenesis, we designed a 39 Mb custom capture panel targeting 17 HPV types and 522 mutant genes related to cervical cancer. Using capture-based next-generation sequencing, HPV integration status, somatic mutation and copy number variation were analyzed on 34 paired samples, including 10 cases of HPV infection (HPV+), 10 cases of cervical intraepithelial neoplasia (CIN) grade and 14 cases of CIN2+ (CIN2: n = 1; CIN2-3: n = 3; CIN3: n = 9; squamous cell carcinoma: n = 1). Finally, the machine learning algorithm (Random Forest) was applied to build the risk stratification model for cervical precursor lesions based on CIN2+ enriched biomarkers. Generally, HPV integration events (11 in HPV+, 25 in CIN1 and 56 in CIN2+), non-synonymous mutations (2 in CIN1, 12 in CIN2+) and copy number variations (19.1 in HPV+, 29.4 in CIN1 and 127 in CIN2+) increased from HPV+ to CIN2+. Interestingly, 'common' deletion of mitochondrial chromosome was significantly observed in CIN2+ (P = 0.009). Together, CIN2+ enriched biomarkers, classified as HPV information, mutation, amplification, deletion and mitochondrial change, successfully predicted CIN2+ with average accuracy probability score of 0.814, and amplification and deletion ranked as the most important features. Our custom capture sequencing combined with machine learning method effectively stratified the risk of cervical lesions and provided valuable integrated triage strategies.