Wang Ting, Zeng Xi, Li Weiyang, Zhu Haijun, Wang Guan, Liu Xiao, Lv Yonggang, Wu Jinghua, Zhuang Xuehan, Zhang Juliang, Zhao Yi, Huang Haodong, Fan Jing, Yao Qing, He Chenyang, Zhang Xiuqing, Huang Chen, Chen Jianghao, Wang Ling
Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi An, China.
BGI-Shenzhen, Shenzhen, China; Division of Genomics and Bioinformatics, CUHK-BGI Innovation Institute of Trans-omics, The Chinese University of Hong Kong, Hong Kong, China.
PLoS One. 2014 Mar 10;9(3):e90343. doi: 10.1371/journal.pone.0090343. eCollection 2014.
Despite an increase in the number of molecular epidemiological studies conducted in recent years to evaluate the association between human papillomavirus (HPV) and the risk of breast carcinoma, these studies remain inconclusive. Here we aim to detect HPV DNA in various tissues from patients with breast carcinoma using the method of HPV capture combined with massive paralleled sequencing (MPS). To validate the confidence of our methods, 15 cervical cancer samples were tested by PCR and the new method. Results showed that there was 100% consistence between the two methods.DNA from peripheral blood, tumor tissue, adjacent lymph nodes and adjacent normal tissue were collected from seven malignant breast cancer patients, and HPV type 16 (HPV16) was detected in 1/7, 1/7, 1/7 and 1/7 of patients respectively. Peripheral blood, tumor tissue and adjacent normal tissue were also collected from two patients with benign breast tumor, and 1/2, 2/2 and 2/2 was detected to have HPV16 DNA respectively. MPS metrics including mapping ratio, coverage, depth and SNVs were provided to characterize HPV in samples. The average coverage was 69% and 61.2% for malignant and benign samples respectively. 126 SNVs were identified in all 9 samples. The maximum number of SNVs was located in the gene of E2 and E4 among all samples. Our study not only provided an efficient method to capture HPV DNA, but detected the SNVS, coverage, SNV type and depth. The finding has provided further clue of association between HPV16 and breast cancer.
尽管近年来进行了越来越多的分子流行病学研究来评估人乳头瘤病毒(HPV)与乳腺癌风险之间的关联,但这些研究仍无定论。在此,我们旨在使用HPV捕获结合大规模平行测序(MPS)的方法,检测乳腺癌患者各种组织中的HPV DNA。为验证我们方法的可信度,用PCR和新方法检测了15份宫颈癌样本。结果显示两种方法的一致性为100%。收集了7例乳腺癌患者的外周血、肿瘤组织、邻近淋巴结和邻近正常组织的DNA,分别在1/7、1/7、1/7和1/7的患者中检测到16型HPV(HPV16)。还收集了2例乳腺良性肿瘤患者的外周血、肿瘤组织和邻近正常组织,分别在1/2、2/2和2/2的样本中检测到HPV16 DNA。提供了包括比对率、覆盖度、深度和单核苷酸变异(SNV)在内的MPS指标来表征样本中的HPV。恶性和良性样本的平均覆盖度分别为69%和61.2%。在所有9个样本中鉴定出126个SNV。所有样本中,SNV数量最多的位于E2和E4基因。我们的研究不仅提供了一种捕获HPV DNA的有效方法,还检测了SNV、覆盖度、SNV类型和深度。这一发现为HPV16与乳腺癌之间的关联提供了进一步线索。