DNA methylation of polycomb group target genes in cores taken from breast cancer centre and periphery

Evangelia-Ourania Fourkala (1) , Cornelia Hauser-Kronberger (2) , Sophia Apostolidou (1) , Matthew Burnell (1) , Allison Jones (1) , Johannes Grall (2) , Roland Reitsamer (3) , Heidi Fiegl (4) , Ian Jacobs (1) , Usha Menon (1) , Martin Widschwendter (1)

1 Department of Gynaecological Oncology, Institute for Women's Health
2 Department of Pathology, Breast Centre Salzburg
3 Department of Senology, Breast Centre Salzburg
4 Department of Gynaecology and Obstetrics

We previously demonstrated that methylation of neugogenic differentiation 1 () gene, a polycomb group target (PCGT) gene is a predictor of response to neoadjuvant chemotherapy in breast cancer. Here, we address the question whether methylation provides clinical information independent from its expression level, and whether PCGT methylation is homogeneous in breast cancer. We examined: (1) methylation and mRNA expression in 9 breast cancer cell lines and 63 tumour specimens, (2) DNA methylation in a training set of 55 PCGT genes taken from the centre (TUC) and periphery (TUP) of 15 breast cancer specimens, and compared this with 22 non neoplastic controls, and finally, (3) validated statistically significant genes in an independent set of 20 cases versus 18 controls. 8/9 cell lines demonstrated methylation, whereas, there was only one cell-line that showed expression. There was no association between methylation and expression in breast tumour specimens, with only 14% exhibiting expression. Of the 55 PCGT genes analysed, 24% (13/55) were shown to be cancer specific ( < 0.05) with a receiver-operating-characteristic (ROC) area-under-the-curve (AUC) of >0.7 (range 0.71–0.95). DNA methylation accurately predicted the presence of cancer in both TUC and TUP. DNA methylation of PCGT genes predicts the presence of breast cancer and is not subject to tumour heterogeneity. Further work will reveal if methylation of PCGT genes will serve as a robust means for the clinical detection and assessment of breast cancer.

Mots clés: DNA methylation; Breast cancer; Intra-tumour heterogeneity

Evangelia-Ourania Fourkala, Cornelia Hauser-Kronberger, Sophia Apostolidou, Matthew Burnell, Allison Jones, et al.. DNA methylation of polycomb group target genes in cores taken from breast cancer centre and periphery. Breast Cancer Research and Treatment, 2009, 120 (2), pp.345-355. ⟨10.1007/s10549-009-0384-3⟩. ⟨hal-00535355⟩