Announcing our Summer Oncology Mini Grant Recipient
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Associate Professor Daniel Buchanan
Congratulations to Associate Professor Daniel Buchanan!
We are delighted to announce that Associate Professor Daniel Buchanan has won our Summer Oncology Genotyping Mini Grant competition! As the recipient of the Mini Grant, which is presented in partnership with Illumina, Assoc. Prof. Buchanan will receive a Methylation EPIC genotyping array run at AGRF, to further his research. He said, ‘I’m very excited about the AGRF mini grant award and how it will enable us to profile the “Methylome” of a rare subtype of colorectal cancers that prove to be diagnostically challenging with current testing approaches. We hope this new methylome information will lead to novel diagnostic methods.’
Assoc. Prof. Buchanan is Head of the Buchanan laboratory: The Colorectal Oncogenomics Group, University of Melbourne Centre for Cancer Research, and will use this grant to assist his research in identifying mendelian-inherited germline mutations that result in colorectal cancer, which is the third-most diagnosed cancer in Australia and accounts for an average of 300 new cases each week. He explained, ‘several studies have highlighted the pivotal role of the complex crosstalk between genetic and epigenetic mechanisms during CRC tumourigenesis. We have shown that genome-wide DNA methylation can explain the CRC tumour heterogeneity and has a promising potential to determine the origin of the tumour and to understand its carcinogenic pathway.
‘Our existing DNA methylation data supports that genome-wide methylation patterns of tumours arisen from specific inherited genetic defects differ from those arisen sporadically. To date, we have tested >700 CRCs using the 450k and EPIC arrays, including those from people with Lynch syndrome and other hereditary CRC subtypes. However, we have not been able to test an important rare subtype of CRC caused by constitutional MLH1 hypermethylation (MLH1 epimutation). MLH1 epimutation carriers develop multiple primary cancers, predominantly CRC, and therefore their identification is important for future cancer prevention. We have collected the CRC tumour DNA from MLH1 epimutation carriers that would be tested on the EPIC array as part of this AGRF project,’ Assoc. Prof. Buchanan said.
Our Genotyping Supervisor Melinda Ziino added, ‘AGRF’s Genotyping Team processes thousands of Methylation EPIC samples each year and we are excited to share our expertise on this project, to further research into colorectal cancer.”
How will AGRF Genotyping benefit colorectal cancer research?
When asked how AGRF Genotyping will benefit his important research, Assoc. Prof. Buchanan said, ‘we will use the EPIC genotyping array to perform genome-wide methylation profiling of CRC tumours from rare MLH1 epimutation carriers. Unlike its synonymous form caused due to tumour specific hypermethylation of MLH1 of a sporadic nature, the MLH1 epimutation carriers can be characterised by soma-wide hypermethylation of MLH1, meaning that this aberration affects every cell in the body. The MLH1 epimutation is extremely rare and current clinical detection still relies on low-resolution and locus-specific profiling of the MLH1 promoter region in multiple tissue types. This often causes equivocal results, albeit patients with MLH1 epimutations need to opt-in for specific clinical management program requiring more frequent screening.
‘We hypothesise that MLH1 epimutation-associated tumours have distinct genome-wide methylation characteristics when compared with sporadic MLH1 methylated and tumours of other subgroups. The data generated from this EPIC genotyping array will be implemented into our machine learning algorithms and transformed into a clinically-applicable MLH1 epimutation score. The addition of EPIC array data from these MLH1 epimutation carrier tumours would enable us to refine our analysis to ensure a future diagnostic test can identify all relevant subtypes of CRC, he explained. We look forward to hearing more about this exciting research!
Our Whole Genome Methylation Screening Service
Screen a human whole genome methylation pattern to identify variable genomic regions that may be contributing to gene expression variation or the phenotypic outcome. Key highlights:
Incorporates miRNA promoter regions
Uses the Illumina Methylation EPIC BeadChip, containing over 850,000 methylation sites
Contains > 90% original content from the broadly used Infinium Human Methylation 450K plus a significant increase in enhancer sites to deliver a comprehensive genome overview
Quantitative analysis at single-nucleotide resolution
Multiple samples can be analysed in parallel from low sample input (as little as 250ng) to deliver high throughput power while minimising the cost per sample.
Read more about our clinical applications on our Clinical Testing page.
