Resolving Suspected Lynch Syndrome Cases to Improve Risk Stratification

ROMY WALKER
PhD Student
Colorectal Oncogenomics Group, Department of Clinical Pathology
University of Melbourne Centre for Cancer Research

Colorectal cancer (CRC) is a major health burden in Australia with individuals having an estimated 5.3% risk of developing CRC during their lifetime. Unfortunately, for 1 in 64 people this diagnosis is fatal. Heritable forms of CRC are most commonly caused by Lynch syndrome, an autosomal dominant disorder presenting with a DNA mismatch repair deficient / microsatellite unstable (dMMR) phenotype. People with Lynch syndrome are predisposed to CRC, endometrial cancers (EC) and sebaceous skin lesions (SSL), as well as other extra-colonic tumours, with affected individuals often developing multiple tumours. Currently, universal testing of all newly diagnosed CRCs and ECs is recommended to detect cancers presenting with dMMR and thus helps with Lynch syndrome identification. However, not all dMMR tumours are caused by Lynch syndrome with some resulting from somatic defects, such as MLH1 promoter hypermethylation, double somatic mutations in MMR genes or where the cause of cancer remains unknown (suspected Lynch syndrome, SLS). These so-called Lynch syndrome mimics make the identification of LS within cancer-affected patients clinically challenging involving a multi-step process to successfully resolve the underlying aetiology.

In this PhD completion seminar, Romy presents a novel approach to help resolve unexplained SLS cases as well as investigates tumour features derived from next-generation sequencing data for their ability to detect dMMR in multiple tissue types. Together, this provides a clinically important tool that can be used to triage people with Lynch syndrome and aid with clinical management of patients and relatives with the highest risk of developing cancer. Romy's PhD project focusses on establishing and implementing novel diagnostic approaches for risk stratification of individuals with mismatch repair-deficient cancers.

Romy Walker is a molecular biologist with a strong background in clinical genetics. After completing her B.Sc. and M.Sc. degrees at the University Hospital Regensburg in Germany, she obtained a position in the Diagnostics Department, focusing on hereditary cancers and rare eye diseases. During her 4-year tenure at the Institute of Human Genetics, she enrolled in an advanced training program offered by The German Society of Human Genetics. This 5-year educational program allows scientists certified as “clinical genetic laboratory specialists” to work as professionals in clinical genetics and patients care. After completing her major in molecular genetics (3 years) at the beginning of 2018, she started a PhD under the supervision of Associate Professor Daniel Buchanan.