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Tissue handling for molecular pathology: a topic of increasing importance

Louise Jones and Clare Craig reflect on the outputs of a workshop held last year, which looked at how best to handle surgical specimens from the point of removal, such that optimal results will be obtained from molecular analysis as well as conventional microscopy and immunohistochemistry.

Cellular pathologists, biomedical scientists and others involved in establishing genomic testing for cancer as part of The 100,000 Genomes Project are facing a number of challenges that come with the rapid progress in molecular diagnos­tics for cancer, including whole genome sequencing (WGS). One key issue is the need to optimise and standardise tissue handling in order to achieve high-quality sequencing while retaining adequate mor­phology for diagnosis. In the Chief Medical Officer for England’s annual report, Professor Dame Sally Davies has emphasised that cancer genomics should become part of routine care. This presents challenges but also potential opportunities.1

During the pilot and initiation implementation phases of The 100,000 Genomes Project, extensive experimental work was undertaken to optimise and standardise the process of formalin fixation and to adapt the DNA extraction process to mini­mise DNA damage. However, while there was some improvement seen, WGS on formalin-fixed paraffin wax-embedded (FFPE) tissue continued to be substantially suboptimal, leading to the conclusion that, for optimal WGS, fresh tissue is required.

What does formalin do to DNA?

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