Page 80 - University of Pretoria Research Review 2017

78
Whole genome sequencing advances cancer research
Vanessa Hayes and Riana Bornman, School of Health Systems and Public Health
Prostate cancer has the highest incidence of all male-associated cancers and the second highest mortality rate in the western world. In most African countries, the incidence of prostate cancer is uncertain, while in South Africa it is estimated that at least one in every 23 men will develop prostate cancer within their lifetime.
Researchers at UP’s School of Health Systems and Public Health have collaborated with the Garvan Institute of Medical Research and the University of Sydney in Australia to, for the first time, map the entire genome of a prostate cancer tumour.
The team, led by Professor Vanessa Hayes, Extraordinary Professor at UP’s School of Health Systems and Public Health, and Head of the Human Comparative and Prostate Cancer Genomics Laboratory at the Garvan Institute, published their findings in the journal Oncotarget in March 2017. The study views the disease through an entirely new lens. Professor Riana Bornman, Senior Research Professor at the School of Health Systems and Public Health, and one of the co- authors of this paper, has been researching prostate cancer, specifically among African men, for many years and has been collaborating with Professor Hayes.
Very little is understood about the genetic drivers of prostate tumours, despite the fact that prostate cancer has been well researched. The treatment of prostate cancer is complicated by the difficulties associated
with identifying tumours that are going to spread and become life-threatening, as opposed to benign tumours, which spare patients harsh and unnecessary treatments.
Significantly, using next-generation mapping technology in combination with whole genome sequencing, the researchers uncovered the most complete picture of prostate cancer’s genomic landscape to date. They studied a prostate tumour from a South African
man with a Gleason score of 7, the most commonly diagnosed form of prostate cancer, which is clinically
Riana Bornman
highly unpredictable.
They eventually identified 85 large structural rearrangements, more than a third of which have
a direct impact on genes known to have cancer- promoting potential. The team uncovered ten times more chromosome genomic rearrangements than previously detected with older technology. The study proves that next-generation mapping is feasible for cancer studies and has potential clinical utility for prognosis, diagnosis and therapy. Next-generation mapping may also eventually help to define African- specific risk areas and the genomic signature of prostate cancer in (south) African men.
The team says that it is unlikely that sequencing technology alone would have produced
these results. While whole genome
sequencing is able to identify small DNA mutations, it may not detect
complete gene deletions, transfers to other chromosome,
or gene
multiplications –
all of which were found in this mapping study.