Publications by authors named "Helen Marfan"
Background: MLH1 epimutation is characterised by constitutional monoallelic MLH1 promoter hypermethylation, which can cause colorectal cancer (CRC). Tumour molecular profiles of MLH1 epimutation CRCs were used to classify germline MLH1 promoter variants of uncertain significance and MLH1 methylated early-onset CRCs (EOCRCs). Genome-wide DNA methylation and somatic mutational profiles of tumours from two germline MLH1: c.
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- Routine screening for DNA mismatch repair (MMR) deficiency in certain tumors often results in unresolved cases labeled as suspected Lynch syndrome (SLS), with a study involving 135 such cases across Australia and New Zealand.
- Targeted sequencing of tumors and matched blood samples revealed that 86.9% of these SLS cases could be classified into specific subtypes, primarily through the detection of double somatic MMR mutations.
- The research indicates that implementing tumor-focused testing and MLH1 methylation assays in clinical settings can effectively clarify SLS diagnoses, leading to better surveillance and screening for patients.
Article Synopsis
- Routine screening for DNA mismatch repair deficiency in colorectal, endometrial, and sebaceous skin tumors has led to many unresolved cases suspected of Lynch syndrome, affecting 135 patients across Australia and New Zealand.
- Targeted panel sequencing of tumors and matched blood DNA helped resolve 86.9% of these suspected cases by identifying various factors, including epimutations and germline MMR variants, with double somatic mutations being the most common cause.
- The study suggests that incorporating tumor sequencing and methylation assays into clinical diagnostics could reduce unresolved cases and improve patient surveillance and screening strategies.
Aim: We aimed to describe and analyse clinical features, characteristics, and adherence to surveillance guidelines in an Australian Birt-Hogg-Dubé syndrome (BHD) and hereditary leiomyomatosis and renal cell cancer (HLRCC) cohort.
Methods: All identified patients with a diagnosis of BHD or HLRCC at RBWH 01/01/2014-01/09/2019 were included (HREC/17/QRBW/276). All patients were initially assessed and counselled by a clinical geneticist and then referred to an adult nephrologist.
Background: Until recently, determining penetrance required large observational cohort studies. Data from the Exome Aggregate Consortium (ExAC) allows a Bayesian approach to calculate penetrance, in that population frequencies of pathogenic germline variants should be inversely proportional to their penetrance for disease. We tested this hypothesis using data from two cohorts for succinate dehydrogenase subunits A, B and C () genetic variants associated with hereditary pheochromocytoma/paraganglioma (PC/PGL).
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