Cancer

Prostate Cancer

Prostate cancer is one of the most common forms of cancer and has a complex genetic etiology. In recent years, the number of genes associated with prostate cancer has grown dramatically in particular due to high throughput techniques like GWAS. However, to date, only one gene, PTEN, has recapitulated prostate cancer in a single gene knockout mouse model. Validating these genetic associations will help understand the fundamental mechanisms of cancer and lead to better diagnoses and therapies.

During my postdoctoral work, we identified one subject, known as DGAP056, who had a constellation of congenital abnormalities as well as early onset prostate cancer (diagnosed at age 38). Karyotyping and sequence identified a chromosomal translocation that disrupts a poorly annotated gene, LDAH (i.e., C2orf43). Using our approach, we discovered several lines of convergent genomic evidence associating prostate cancer with LDAH, including evidence from GWAS, microarray/RNASeq and prostate cell lines. Based on this evidence, we developed a Ldah knockout mouse model which successfully recapitulated prostate cancer. Our goal is now to understand how disruption of the cholesterol esterase function of Ldah leads to prostate and other forms of cancer.