David Bowtell, PhD
Peter MacCallum Cancer Center
2011–2013 Lester and Bernice Smith Fellow
Challenge Grant Award Recipient – 2011
Circulating TP53 mutations as a biomarker of high-grade serous cancer
In his proposed project, Dr. Bowtell will use the latest, most sensitive DNA sequencing techniques to study whether ovarian cancer tumors give off enough DNA into circulating blood to use as an early detection tool. Specifically, the TP53 gene will be examined. Damage to the TP53 gene occurs in essentially 100% of serous ovarian cancers, the most common type of fatal ovarian cancer, and occurs early in the development of the disease. In fact, TP53 mutation is the earliest molecular lesion yet identified in high grade serous cancers, present in intense staining of the fallopian tubes called “p53 signatures” This finding agrees with the most current understanding of serous ovarian cancer which places the origin of this cancer at the fallopian tubes rather than in the ovaries. As a tumor grows, some cells die and release their DNA into circulating blood, including DNA encoding mutated genes. The proposed project by Dr. Bowtell will determine whether circulating TP53 can be detected in circulating blood using advanced genomic techniques. If successful, this novel approach will provide an important diagnostic tool for early detection of serous ovarian cancer – the most common and deadly type of ovarian cancer.