L. Spans PhD, E. Lerut MD, PhD, S. Joniau MD, PhD, F. Claessens PhD
Whole exome sequencing was performed on 38 high-risk prostate cancer samples. We confirmed recurrent mutations in prostate cancer-specific genes, but also identified genes not reported to be mutated, like TET1. This DNA hydroxymethylase converts methylcytosines to hydroxymethylcytosines as a first step in DNA demethylation. By immunohistochemistry, we detected decreased TET1 protein levels in tumour compared to surrounding non-tumour tissue. DNA hydroxymethylation followed the same course. Furthermore, TET1 mRNA expression levels are an independent predictor of metastasis-free survival in a larger retrospective cohort, indicating an important role for TET1 and hydroxymethylation in prostate cancer.
The LNCaP and C4-2B cell lines form an excellent preclinical model to study the development of metastatic castration-resistant prostate cancer. Both exome and transcriptome sequencing was performed: more than half of the mutations found in the exomes were confirmed in the RNA-sequencing data. Combining C4-2B-specific mutations with differentially expressed genes allowed the detection of changes in focal adhesion and ECM-receptor interactions, which might contribute to the metastatic potential of C4-2B cells.