European Translational Oncology Prevention and Screening (EUTOPS) Institute, 6060, Hall in Tirol, Austria.
Research Institute for Biomedical Aging Research, Universität Innsbruck, 6020, Innsbruck, Austria.
Nat Commun. 2022 Feb 1;13(1):448. doi: 10.1038/s41467-021-26615-y.
The vast majority of epithelial ovarian cancer arises from tissues that are embryologically derived from the Müllerian Duct. Here, we demonstrate that a DNA methylation signature in easy-to-access Müllerian Duct-derived cervical cells from women with and without ovarian cancer (i.e. referred to as the Women's risk IDentification for Ovarian Cancer index or WID-OC-index) is capable of identifying women with an ovarian cancer in the absence of tumour DNA with an AUC of 0.76 and women with an endometrial cancer with an AUC of 0.81. This and the observation that the cervical cell WID-OC-index mimics the epigenetic program of those cells at risk of becoming cancerous in BRCA1/2 germline mutation carriers (i.e. mammary epithelium, fallopian tube fimbriae, prostate) further suggest that the epigenetic misprogramming of cervical cells is an indicator for cancer predisposition. This concept has the potential to advance the field of risk-stratified cancer screening and prevention.
绝大多数上皮性卵巢癌起源于胚胎时期源自 Müllerian 管的组织。在这里，我们证明了患有和不患有卵巢癌的女性容易获取的 Müllerian 管衍生宫颈细胞中的 DNA 甲基化特征（即称为女性卵巢癌风险识别指数或 WID-OC-index）能够在没有肿瘤 DNA 的情况下识别出患有卵巢癌的女性，其 AUC 为 0.76，并且能够识别出患有子宫内膜癌的女性，其 AUC 为 0.81。这一观察结果以及宫颈细胞 WID-OC-index 模拟了那些在 BRCA1/2 种系突变携带者中具有癌变风险的细胞的表观遗传程序（即乳腺上皮、输卵管纤毛、前列腺），进一步表明宫颈细胞的表观遗传编程错误是癌症易感性的指标。这一概念有可能推动风险分层癌症筛查和预防领域的发展。
