Detection of breast and ovarian cancer using epigenetic features in cervical samples

Really excited to announce that my joint-first author paper, looking at DNA methylation in cervical screening samples to detect/risk predict breast cancer, was published in Nature Communications today: The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples.

It’s part of two papers from our group appearing in Nature Communications today, where we describe the potential of cervical screening samples for individualised risk prediction and detection of breast and ovarian cancer.

Behind the paper article

Twitter 🧵

Routine cervical screening samples have the potential to detect breast and ovarian cancer using DNA methylation 🧬

A 🧵 on our two papers out in @NatureComms today...https://t.co/GYzlppuTkZ
— Dr Chiara Herzog (@chiara_herzog) February 1, 2022

References

2022

The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples

James E. Barrett*, Chiara Herzog*, Allison Jones, and 22 more authors

Nature Communications, 2022

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Genetic and non-genetic factors contribute to breast cancer development. An epigenome-based signature capturing these components in easily accessible samples could identify women at risk. Here, we analyse the DNA methylome in 2,818 cervical, 357 and 227 matched buccal and blood samples respectively, and 42 breast tissue samples from women with and without breast cancer. Utilising cervical liquid-based cytology samples, we develop the DNA methylation-based Women’s risk IDentification for Breast Cancer index (WID-BC-index) that identifies women with breast cancer with an AUROC (Area Under the Receiver Operator Characteristic) of 0.84 (95% CI: 0.80–0.88) and 0.81 (95% CI: 0.76–0.86) in internal and external validation sets, respectively. CpGs at progesterone receptor binding sites hypomethylated in normal breast tissue of women with breast cancer or in BRCA mutation carriers are also hypomethylated in cervical samples of women with poor prognostic breast cancer. Our data indicate that a systemic epigenetic programming defect is highly prevalent in women who develop breast cancer. Further studies validating the WID-BC-index may enable clinical implementation for monitoring breast cancer risk. Breast cancer is most commonly diagnosed via a needle biopsy. In this study, the authors show that cervical samples from women with breast cancer have a methylation signature different to that of healthy controls.
The DNA methylome of cervical cells can predict the presence of ovarian cancer

James E. Barrett, Allison Jones, Iona Evans, and 10 more authors

Nature Communications, 2022

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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. Most ovarian cancers originate from cells originally derived from Müllerian Duct cells. Here, the authors show that the methylation profile of Müllerian Duct cells isolated from cervical samples can predict whether a woman has cervical cancer.

Detection of breast and ovarian cancer using epigenetic features in cervical samples

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References

2022

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