Resolving Suspected Lynch Syndrome Cases to Improve Risk Stratification | Romy Walker

An improved approach to resolve DNA mismatch repair deficient colorectal and endometrial cancers classified as suspected Lynch syndrome through targeted tumour sequencing and multiple MLH1 promoter methylation assays.

Romy Walker
PhD student, Colorectal Oncogenomics
Department of Clinical Pathology
University of Melbourne Centre for Cancer Research

20 May 2020

Lynch syndrome (LS) is an inherited disorder predisposing to colorectal (CRC) and endometrial cancer (EC). It is of major clinical significance to identify individuals who carry a mutation for this syndrome as routine surveillance considerably improves survival through early cancer detection. CRCs/ECs from individuals with LS have a heritable defect in their DNA mismatch repair (MMR) machinery evidenced by loss of MMR protein expression and microsatellite instability. Diagnosing people with LS can be difficult as there are other MMR-deficient subtypes with similar tumour characteristics including MLH1 promoter hypermethylated tumours and suspected LS (SLS), where the cause for MMR-deficiency still remains largely unknown.

Being able to accurately differentiate between these subtypes has a high clinical impact on the risk assessment and surveillance of affected patients and their at-risk relatives. However, current testing techniques still fall short of effectively stratifying these MMR-deficient subtypes due to similar prevalence rates, histopathological- and clinical features.

Romy presents an improved diagnostic testing strategy that can effectively differentiate inherited from sporadic causes of MMR-deficiency through a combined approach of targeted tumour sequencing and application of two independent MLH1 methylation assays.

Romy Walker is a molecular biologist with a strong background in clinical genetics. Beginning 2018, Romy has completed her major in molecular genetics (3 years) and has started a PhD under the supervision of Associate Professor Daniel Buchanan. Her research focuses on establishing and implementing novel diagnostic approaches for risk stratification of individuals with mismatch repair-deficient cancer.