Superior gene sequencing: accelerating the route towards personalised cancer treatment
Accurate and complete gene sequencing in tumors is increasingly relevant for cancer diagnosis, prognosis and treatment decisions. The project SuperGeneSeq, carried out in partnership between the research group of Wouter de Laat at the Hubrecht Institute and biotech company Cergentis, had the aim to develop novel methodologies for improved genetic analysis of disease genes in fixed tumor samples.
Already for decades fixation and embedding is the pathologist’s method of choice to secure and store tumor samples. However, due to this treatment DNA in these samples is damaged and fragmented, compromising genetic analysis. Yet this is needed since mutations occur frequently in cancer and increasingly serve as targets for precision medicine. The development of a robust genetic analysis method to sequence selected target genes in fixed tumor specimens therefore holds great promise as a companion diagnostic for personalised medicine.
The hypothesis was that Cergentis’ proprietary physical proximity technologies may well be the methods of choice for targeted genetic analysis in fixed tumor samples, as these technologies rely on fixation and DNA fragmentation. In parallel, the proposal was to develop a novel concept that uses gene editing and bacterial DNA amplification for targeted sequencing of genes that for technical reasons currently are difficult to analyse in the clinic.
In this project, proof-of-concept was showed that this novel method enables targeted sequencing of such genes. Also, it was demonstrated that Cergentis’ methodologies enable gene rearrangement detection in fixed tumor samples. In a pilot experiment comparing these methods to the current golden standard method in the clinic, it scored the previously identified rearrangements but additionally found multiple new clinically relevant rearrangements. As a next step towards clinical implementation a larger validation study is ongoing.
