Research Associate ProfessorMSc(Hons) (Canterbury), PhD (Otago)
Rutherford Discovery Fellow
Co-ordinator, New Zealand Familial Breast Cancer Study
Tel 64 3 364 0544
Associate Professor Logan Walker's primary research is focused on understanding how genetic changes cause an increased risk of cancer and/or affect tumour pathology.
Genetic variation and breast cancer development
Breast cancer is the most common cancer in women yet for most women the genetic changes underlying their disease remain undetermined or poorly understood. This research aims to determine the clinical and biological impact of:
- DNA sequence variants in known breast cancer susceptibility genes (eg. BRCA1 and BRCA2)
- DNA copy number variants across the genome, in breast cancer development
The New Zealand Familial Breast Cancer Study commenced in 2013 with the key goal of better understanding DNA sequence changes in genes that alter the risk of developing breast cancer. Genetic testing of breast cancer susceptibility genes, BRCA1 and BRCA2, has become common practice for patients with a strong family history of the disease. However, a significant proportion of tests result in the detection of a genetic change for which disease association is not known. This study will address this important issue through collaborative links with the international scientific consortia, ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) and CIMBA (Consortium of Investigators of Modifiers of BRCA1/2).
The role of germline copy number variation in endometrial cancer risk and development
Endometrial cancer is the most common gynaecological cancer in New Zealand and the incidence is increasing as the population ages. Mutations in the mismatch repair genes MLH1, MSH2, MSH6 and PMS2 are known to confer increased risk in a proportion of endometrial cancer cases. There are several other genes encoding proteins that act in the mismatch repair pathway, but evidence for the involvement of these and other genes in endometrial cancer susceptibility is currently limited. We are utilising large genetic datasets to identify common and rare genetic changes in these genes that are associated with endometrial cancer risk.
Molecular markers of prognosis for colorectal cancer patients
Colorectal cancer (CRC) prognosis is currently predicted by clinicopathological stage which confers significant prognostic variability. Substantial progress has occurred in the understanding of the molecular basis of CRC. Molecular techniques offer promise in improving staging and therefore targeting of therapy. However, limitations in current technology have seen few molecular biomarkers implemented in clinical practice. The Mackenzie Cancer Research Group are using a powerful new mRNA in situ hybridisation technology (RNAscope) that measures RNA in histologically preserved cells while overcoming limitations of existing techniques. This research aims to establish RNAscope as a valid method to identify mRNA markers for CRC prognosis.
The BRCA code
Understanding the role of genetic changes, or mutations, to breast and ovarian cancer risk is the focus of Dr Logan Walker.
Walker, L. C., de la Hoya, M., Wiggins, G. A. R., Lindy, A., Vincent, L. M., Parsons, M. T., … & ClinGen Sequence Variant Interpretation Working Group. (2023). Using the ACMG/AMP framework to capture evidence related to predicted and observed impact on splicing: Recommendations from the ClinGen SVI Splicing Subgroup. American Journal of Human Genetics, 110(7), 1046-1067. doi: 10.1016/j.ajhg.2023.06.002
Jasiak, A., Koczkowska, M., Stukan, M., Wydra, D., Biernat, W., Izycka-Swieszewska, E., … Eccles, M. R., Walker, L., … Ratajska, M. (2023). Analysis of BRCA1 and BRCA2 alternative splicing in predisposition to ovarian cancer. Experimental & Molecular Pathology. Advance online publication. doi: 10.1016/j.yexmp.2023.104856
Holdren, M., Richardson, M., Ritter, D., Young, C., Brannan, T., Pesaran, T., … Walker, L., … Couch, F. (2023). ATM and PALB2 variant curation guidelines progress update: ClinGen Hereditary Breast, Ovarian, and Pancreatic Cancer Variant Curation Expert Panel. Genetics in Medicine Open, 1(1, Suppl.), (pp. 11). doi: 10.1016/j.gimo.2023.100080
Parsons, M., Anderson, M., Berkofsky-Fessler, W., Caputo, S., Chan, R., Cline, M., … Walker, L., … Spurdle, A. (2023). The ClinGen ENIGMA BRCA1/2 expert panel: A dynamic framework for evidence-based recommendations to improve classification criteria for variants in BRCA1/2. Genetics in Medicine Open, 1(1, Suppl.), (pp. 19). doi: 10.1016/j.gimo.2023.100095
Hakkaart, C., Pearson, J. F., Marquart, L., Dennis, J., Wiggins, G. A. R., Barnes, D. R., Robinson, B. A., Mace, P. D., … Walker, L. C. (2022). Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers. Communications Biology, 5, 1061. doi: 10.1038/s42003-022-03978-6