Research Projects

Genetic variation in South African breast cancer patients using genome sequencing – Prof Fourie Joubert

Genetic variation in South African breast cancer patients using genome sequencing – Prof Fourie Joubert

Prof Fourie Joubert

Prof Fourie Joubert

Prof Fourie Joubert

Dept Bioinformatics and Computational Biology Unit, University of Pretoria


Project Title

An investigation into genetic variation in South African breast cancer patients using genome sequencing.

Project Description

Breast cancer is the second most prevalent form of cancer in South Africa. As commonly-identified mutations such as BRCA1 and BRCA2 mutations are often not observed, complete exome sequencing will be used to sequence genomes from selected breast cancer patients for the discovery of novel mutations. There are two work packages, the first entailing the sequencing of family members with breast cancer. Exome sequencing will yield around 30x coverage of approximately 200,000 exomes from these patients. The second work package compares tumour-normal samples in matched black South African patients. Directed sequencing of the tumours will be performed using the Ion Torrent Comprehensive Cancer Panel, followed by complete exome sequencing of the normal tissue. Data will be mapped to the hg19 reference human genome assembly for variant identification and analysis. Selected variants will be further studied in larger sample groups using directed sequencing. Identified variants are of high significance for use in early detection and epidemiology studies, as well as in understanding the functional mechanisms of transformation in these cancers.

Non-scientific report

Two different types of DNA sequencing were used to look at the DNA of sets of breast cancer patients. In the first case, patient sets were selected that are related to each other, and may possibly have the same DNA features that make them susceptible to breast cancer. For the DNA of these patients, all the regions of the genome that encode protein products were sequenced. Following a set of data clean-up procedures, these regions were analyzed for DNA changes that changed the sequence of the protein product, and that occur in proteins that may potentially play a role in cancer. In the case of possibly-interesting changes, confirmation of the changes on a DNA level using an additional DNA sequencing technology has started.

The investigation of the changes detected is currently ongoing. Initially, four potentially interesting mutations were identified and further investigated. Three of them were eliminated but the fourth is undergoing further study.  In the second case, patients were selected where normal and tumor DNA was available, so that changes in the tumor DNA could be detected vs the normal DNA. This proved quite difficult, as the tumor DNA is isolated from paraffin sections made by the pathologists, and this DNA may be degraded. Only some of the samples could successfully be sequenced. Data clean-up was performed, and variants were detected that occur in the tumor, but not in the normal DNA. The analysis emphasized several problems with the data, and new sequencing of the tumor-normal pairs is currently being performed.


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