Establishing Cancer Genomics Registry to Support Implementation of Personalised Medicine
Prof Maritha Kotze
Project ended 31 March 2018
Prof Maritha Kotze
- Department of Pathology, Faculty of Health Sciences, University of Stellenbosch
- E- mail
Title of the project
Establishing a cancer genomics registry to support the implementation of personalised medicine.
Project Description
A database resource for translational oncogenomic research was established during the introduction of a microarray-based gene expression profiling test for early-stage breast carcinoma in South Africa. The ongoing development of this resource has facilitated the development of eligibility criteria and reimbursement policies for this service (MammaPrint). This is comparable to existing referral guidelines for familial breast cancer screening programs focused on high-penetrance BRCA1/2 mutations, using risk assessment tools such as the Manchester score. This study investigated the rationale for incorporating actionable low-moderate penetrance mutations into a novel pre-screen algorithm for selection of breast cancer patients eligible for whole exome sequencing, which is currently lacking in the local setting. Our experience in cancer genetics provided the basis for establishment of a cancer genomics database/registry as a valuable resource for ongoing oncogenomic research.
How the project was of value in the struggle against cancer
Use of the CANSA grant helped to develop the conceptual framework for clinical application of whole exome sequencing (WES) in SA breast cancer patients. Many pathogenic mutations that remained undetected with previous used of tests focused on a limited number of mutations/gene were identified and provided targets for treatment and disease prevention in affected studies.
Our pathology-supported genetic testing (PSGT) platform was used to develop an exome pre-screen algorithm (EPA) for selection of genetically uncharacterised patients for WES. First, diagnostic BRCA testing is offered as a routine service according to standard referral guidelines, or the chronic disease risk screen is offered to patients receiving hormone therapy, are at high risk for tumour recurrence, or are required to take potentially competing antidepressants. In certain cases, combined diagnostic and pharmacogenetics testing is performed to explain the presence of comorbidities or predict drug response/recurrence risk. Finally, where extended mutation analysis of the entire BRCA1 and 2 genes as well as the CYP2D6 gene is unable to explain breast cancer or the occurrence of drug side effects/failure, WES is performed to identify potential novel causative genes/mutations.
WES preceded by PSGT facilitates the identification and clinical interpretation of genetic risk factors of relevance to both cancer development and tailored therapeutic intervention in a single test.
Given the potential of biochemical methods and other health assessments to uncover the genetic component of complex, multifactorial diseases in a clinical context, we envisage a future where research databases establishing cancer genomics registry to support implementation of personalised medicine) are developed in parallel with patient care for differential diagnosis and long-term pharmacogenomics informed clinical outcome studies.
Peer-reviewed publications
- Application of advanced molecular technology in the diagnosis and application of genetic disorders in South Africa – 2016
- Impact of MammaPrint on clinical decision-making in South African patients with early-stage breast cancer – 2016
- Postmenopausal breast cancer, aromatase inhibitors, and bone health: What the surgeon should know – 2016
- Exome sequencing in a family with luminal-type breast cancer underpinned by variation in the methylation pathway -2017
- Pharmacogenetics of aromatase inhibitors in endocrine responsive breast cancer: lessons learned from tamoxifen and CYP2D6 genotyping – 2017
- Reclassification of early-stage breast cancer into treatment groups by combining the use of immunohistochemistry and microarray analysis – 2019
- Baseline bone health status in multi-ethnic South African postmenopausal breast cancer patients at initiation of aromatase inhibitor therapy: A descriptive study – 2019
- The cost impact of unselective vs selective MammaPrint testing in early-stage breast cancer in Southern Africa – 2021
- A View on Genomic Medicine Activities in Africa: Implications for Policy – 2022
