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Dr Logan Walker

Logan WalkerSenior Research Fellow

MSc(Hons) (Canterbury), PhD (Otago)

Rutherford Discovery Fellow
Co-ordinator, New Zealand Familial Breast Cancer Study

Email logan.walker@otago.ac.nz 
Tel 64 3 364 0544

Research Interests

Dr 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:

  1. DNA sequence variants in known breast cancer susceptibility genes (eg. BRCA1 and BRCA2) 
  2. DNA copy number variants across the genome, in breast cancer development

The New Zealand Familial Breast Cancer Study

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.

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Publications

Walker, L. C., Marquart, L., Pearson, J. F., Wiggins, G. A. R., O'Mara, T. A., Parsons, M. T., … Spurdle, A. B. (2017). Evaluation of copy-number variants as modifiers of breast and ovarian cancer risk for BRCA1 pathogenic variant carriers. European Journal of Human Genetics, 25, 432-438. doi: 10.1038/ejhg.2016.203

Walker, L. C., Pearson, J. F., Wiggins, G. A. R., Giles, G. G., Hopper, J. L., & Southey, M. C. (2017). Increased genomic burden of germline copy number variants is associated with early onset breast cancer: Australian breast cancer family registry. Breast Cancer Research, 19(1), 30. doi: 10.1186/s13058-017-0825-6

Shimelis, H., Mesman, R. L. S., Von Nicolai, C., Ehlen, A., Guidugli, L., Martin, C., … Walker, L., … Couch, F. J. (2017). BRCA2 hypomorphic missense variants confer moderate risks of breast cancer. Cancer Research. Advance online publication. doi: 10.1158/0008-5472.can-16-2568

de la Hoya, M., Sourarieh, O., López-Perolio, I., Vega, A., Walker, L. C., van Ierland, Y., … Lattimore, V., … Spurdle, A. B. (2016). Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms. Human Molecular Genetics, 25(11), 2256-2268. doi: 10.1093/hmg/ddw094

Fackenthal, J. D., Yoshimatsu, T., Zhang, B., de Garibay, G. R., Colombo, M., De Vecchi, G., … Walker, L. C., … de la Hoya, M. (2016). Naturally occurring BRCA2 alternative mRNA splicing events in clinically relevant samples. Journal of Medical Genetics, 53, 548-558. doi: 10.1136/jmedgenet-2015-103570

Chapter in Book - Research

Walker, L. C., Nones, K., Patch, A.-M., & Waddell, N. (2016). Studying genomic and epigenetic aberrations by microarray profiling. In Encyclopedia of Life Sciences. Chichester, UK: John Wiley & Sons. doi: 10.1002/9780470015902.a0022417.pub2

Walker, L. C., & Waddell, N. (2010). Studying genomic aberrations by microarray profiling. In Encyclopedia of Life Sciences. Chichester, UK: John Wiley & Sons. doi: 10.1002/9780470015902.a0022417

Walker, L. C., & Spurdle, A. B. (2010). Prioritizing candidate genetic modifiers of BRCA1 and BRCA2 using a combinatorial analysis of global expression and polymorphism association studies of breast cancer. In M. Webb (Ed.), Cancer susceptibility: Methods and protocols (Methods in molecular biology, Vol. 653). (pp. 23-34). New York: Springer. doi: 10.1007/978-1-60761-759-4

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Journal - Research Article

Shimelis, H., Mesman, R. L. S., Von Nicolai, C., Ehlen, A., Guidugli, L., Martin, C., … Walker, L., … Couch, F. J. (2017). BRCA2 hypomorphic missense variants confer moderate risks of breast cancer. Cancer Research. Advance online publication. doi: 10.1158/0008-5472.can-16-2568

Walker, L. C., Pearson, J. F., Wiggins, G. A. R., Giles, G. G., Hopper, J. L., & Southey, M. C. (2017). Increased genomic burden of germline copy number variants is associated with early onset breast cancer: Australian breast cancer family registry. Breast Cancer Research, 19(1), 30. doi: 10.1186/s13058-017-0825-6

Walker, L. C., Marquart, L., Pearson, J. F., Wiggins, G. A. R., O'Mara, T. A., Parsons, M. T., … Spurdle, A. B. (2017). Evaluation of copy-number variants as modifiers of breast and ovarian cancer risk for BRCA1 pathogenic variant carriers. European Journal of Human Genetics, 25, 432-438. doi: 10.1038/ejhg.2016.203

de la Hoya, M., Sourarieh, O., López-Perolio, I., Vega, A., Walker, L. C., van Ierland, Y., … Lattimore, V., … Spurdle, A. B. (2016). Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms. Human Molecular Genetics, 25(11), 2256-2268. doi: 10.1093/hmg/ddw094

Morley-Bunker, A., Walker, L. C., Currie, M. J., Pearson, J., & Eglinton, T. (2016). Translating colorectal cancer genetics into clinically useful biomarkers. Colorectal Disease, 18(8), 749-762. doi: 10.1111/codi.13334

Fackenthal, J. D., Yoshimatsu, T., Zhang, B., de Garibay, G. R., Colombo, M., De Vecchi, G., … Walker, L. C., … de la Hoya, M. (2016). Naturally occurring BRCA2 alternative mRNA splicing events in clinically relevant samples. Journal of Medical Genetics, 53, 548-558. doi: 10.1136/jmedgenet-2015-103570

Gerring, Z., Pearson, J. F., Morrin, H. R., Robinson, B. A., Harris, G. C., & Walker, L. C. (2015). Phosphohistone H3 outperforms Ki67 as a marker of outcome for breast cancer patients. Histopathology, 67(4), 538-547. doi: 10.1111/his.12678

Peterlongo, P., Chang-Claude, J., Moysich, K. B., Rudolph, A., Schmutzler, R. K., Simard, J., … Walker, L. C., … Friedman, E. (2015). Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiology, Biomarkers & Prevention, 24(1), 308-316. doi: 10.1158/1055-9965.epi-14-0532

Richardson, A. K., Currie, M. J., Robinson, B. A., Morrin, H., Phung, Y., Pearson, J. F., … Walker, L. C. (2015). Cytomegalovirus and Epstein-Barr Virus in breast cancer. PLoS ONE, 10(2), e0118989. doi: 10.1371/journal.pone.0118989

Walker, L. C., Wiggins, G. A. R., & Pearson, J. F. (2015). The role of constitutional copy number variants in breast cancer. Microarrays, 4(3), 407-423. doi: 10.3390/microarrays4030407

Moir-Meyer, G. L., Pearson, J. F., Lose, F., The Australian National Endometrial Cancer Study Group, Scott, R. J., McEvoy, M., … Walker, L. C. (2015). Rare germline copy number deletions of likely functional importance are implicated in endometrial cancer predisposition. Human Genetics, 134(3), 269-278. doi: 10.1007/s00439-014-1507-4

Whiley, P. J., de la Hoya, M., Thomassen, M., Becker, A., Brandão, R., Sokilde Pedersen, I., … Lattimore, V., … Walker, L., … on behalf of the ENIGMA consortium. (2014). Comparison of mRNA splicing assay protocols across multiple laboratories: Recommendations for best practice in standardized clinical testing. Clinical Chemistry, 60(2), 341-352. doi: 10.1373/clinchem.2013.210658

Colombo, M., Blok, M. J., Whiley, P., Santamariña, M., Gutiérrez-Enríquez, S., Romero, A., … Walker, L., … de la Hoya, M. (2014). Comprehensive annotation of splice junctions supports pervasive alternative splicing at the BRCA1 locus: A report from the ENIGMA consortium. Human Molecular Genetics, 23(14), 3666-3680. doi: 10.1093/hmg/ddu075

Walker, L. C., McDonald, M., Wells, J. E., Harris, G. C., Robinson, B. A., & Morris, C. M. (2013). Dual-color fluorescence in situ hybridization reveals an association of chromosome 8q22 but not 8p21 imbalance with high grade invasive breast carcinoma. PLoS ONE, 8(7), e70790. doi: 10.1371/journal.pone.0070790

Walker, L. C., Whiley, P. J., Houdayer, C., Hansen, T. V. O., Vega, A., Santamarina, M., … on behalf of the ENIGMA consortium. (2013). Evaluation of a 5-tier scheme proposed for classification of sequence variants using bioinformatic and splicing assay data: Inter-reviewer variability and promotion of minimum reporting guidelines. Human Mutation, 34(10), 1424-1431. doi: 10.1002/humu.22388

Walker, L. C., Krause, L., kConFab Investigators, Spurdle, A. B., & Waddell, N. (2012). Germline copy number variants are not associated with globally acquired copy number changes in familial breast tumours. Breast Cancer Research & Treatment, 134(3), 1005-1011. doi: 10.1007/s10549-012-2024-6

Whiley, P. J., Guidugli, L., Walker, L. C., Healey, S., Thompson, B. A., Lakhani, S. R., … Spurdle, A. B. (2011). Splicing and multifactorial analysis of intronic BRCA1 and BRCA2 sequence variants identifies clinically significant splicing aberrations up to 12 nucleotides from the intron/exon boundary. Human Mutation, 32(6), 678-687. doi: 10.1002/humu.21495

Spurdle, A. B., Thompson, D. J., Ahmed, S., Ferguson, K., Healey, C. S., O'Mara, T., Walker, L. C., … The Australian National Endometrial Cancer Study Group, … National Study of Endometrial Cancer Genetics Group, … Easton, D. F. (2011). Genome-wide association study identifies a common variant associated with risk of endometrial cancer. Nature Genetics, 43(5), 451-454. doi: 10.1038/ng.812

Whiley, P., Pettigrew, C. A., Brewster, B. L., Walker, L. C., for kConFab Investigators, Spurdle, A. B., & Brown, M. A. (2010). Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts. BMC Medical Genetics, 11, 80. doi: 10.1186/1471-2350-11-80

Walker, L. C., Thompson, B. A., Waddell, N., kConFab Investigators, Grimmond, S. M., & Spurdle, A. B. (2010). Use of DNA–damaging agents and RNA pooling to assess expression profiles associated with BRCA1 and BRCA2 mutation status in familial breast cancer patients. PLoS Genetics, 6(2), e1000850. doi: 10.1371/journal.pgen.1000850

Walker, L. C., Whiley, P., Couch, F. J., Farrugia, D. J., Healey, S., Eccles, D. M., … kConFab Investigators, … Spurdle, A. B. (2010). Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence variants encoding missense substitutions: Implications for prediction of pathogenicity. Human Mutation, 31(6), E1484-E1505. doi: 10.1002/humu.21267

Walker, L. C., Fredericksen, Z. S., Wang, X., Tarrell, R., Pankratz, V. S., Lindor, N. M., … Couch, F. J. (2010). Evidence for SMAD3 as a modifier of breast cancer risk in BRCA2 mutation carriers. Breast Cancer Research, 12(6), R102. doi: 10.1186/bcr2785

Walker, L. C., Harris, G. C., Wells, J. E., Robinson, B. A., & Morris, C. M. (2008). Association of chromosome band 8q22 copy number gain with high grade invasive breast carcinomas by assessment of core needle biopsies. Genes Chromosomes & Cancer, 47(5), 405-417. doi: 10.1002/gcc.20545

Waddell, N., Ten Haaf, A., Marsh, A., Johnson, J., Walker, L. C., kConFab Investigators, … Spurdle, A. B. (2008). BRCA1 and BRCA2 missense variants of high and low clinical significance influence lymphoblastoid cell line post-irradiation gene expression. PLoS Genetics, 4(5), e1000080. doi: 10.1371/journal.pgen.1000080

Walker, L. C., Waddell, N., Ten Haaf, A., kConFab Investigators, Grimmond, S., & Spurdle, A. B. (2008). Use of expression data and the CGEMS genome-wide breast cancer association study to identify genes that may modify risk in BRCA1/2 mutation carriers. Breast Cancer Research & Treatment, 112(2), 229-236. doi: 10.1007/s10549-007-9848-5

Walker, L. C., Harris, G. C., Holloway, A. J., McKenzie, G. W., Wells, J. E., Robinson, B. A., & Morris, C. M. (2007). Cytokeratin KRT8/18 expression differentiates distinct subtypes of grade 3 invasive ductal carcinoma of the breast. Cancer Genetics & Cytogenetics, 178, 94-103.

Ganly, P. S., Walker, L. C., & Morris, C. M. (2004). Familial mutations of the transcription factor RUNX1 (AML1, CBFA2) predispose to acute myeloid leukemia. Leukemia & Lymphoma, 45(1), 1-10.

Walker, L. C., Campbell, H. J., Corbett, R., Spearing, R. L., Heaton, D. C., Macdonald, D. H., Morris, C. M., & Ganly, P. S. (2002). A novel inherited mutation of the transcription factor RUNX1 causes thrombocytopenia and may predispose to acute myeloid leukaemia. British Journal of Haematology, 117(4), 878-881. doi: 10.1046/j.1365-2141.2002.03512.x

Walker, L. C., Morrison, M. J., Parfitt, R., & Crossen, P. E. (2001). Translocation (2;14) associated with complex rearrangements of the Ig heavy chain in non-Hodgkin lymphoma. Cancer Genetics & Cytogenetics, 128, 137-140.

Sin, F. T. Y., Mukherjee, U. K., Walker, L. C., & Sin, I. L. (1997). The application of gene transfer techniques to marine resource mangement: Recent advances, problems and future directions. Hydrobiologia, 352, 263-278.

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Journal - Research Other

Lattimore, V., Currie, M., Lintott, C., Sullivan, J., Robinson, B. A., & Walker, L. C. (2015). Meeting the challenges of interpreting variants of unknown clinical significance in BRCA testing. New Zealand Medical Journal, 128(1419). Retrieved from http://www.nzma.org.nz/journal

Walker, L. C. (2009). Toward understanding the molecular basis of ovarian cancer. Human Mutation, 30(12), v. doi: 10.1002/humu.21162

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