In a recent paper published in the Briefings in Bioinformatics, the authors discuss bioinformatics approaches to next-generation sequencing (NGS)-based precision oncology, including variant calling, annotation, interpretation, drug matching and reporting in a molecular tumor board setting. The article describes the workflow of a molecular tumor board and the specific bioinformatics support that it requires, from the primary analysis of raw molecular profiling data to the automatic generation of a clinical report and its delivery to decision-making oncologists.

Such bioinformatics workflows have to various degrees been implemented in many clinical trials, as well as in molecular tumour boards at specialised cancer centres and university hospitals worldwide. The goal is to profile the genetic aberrations of tumors such as single-nucleotide variants, copy number variants, insertions and deletions, structural variants and gene fusions, and to suggest potential molecular-based treatments. These approaches can be organised either as a single institutional molecular tumor board or as a basket trial.

Molecular tumor boards are now widespread in the USA, Europe and Australia with reported patient numbers to date ranging up to 2000 patients per cancer center. Ideally, a biopsy is taken on tumor progression from the last therapy to resemble the current genetic state of the evolved tumor. However, some molecular tumor board approaches also profile biopsies sampled at diagnosis.

The NGS data are analyzed for genetic aberrations and potential drug interactions. Specific treatment suggestions are incorporated into a clinical report, which together with the patient’s clinical data, such as treatment history, comorbidities and radiology scans, forms the basis for therapeutic decision-making in an interdisciplinary molecular tumor board. The molecular report may suggest tumor genotype-matched clinical trials and targeted therapies or recommend the avoidance of drugs in cases where mutations that potentially confer treatment resistance have been detected.

A number of challenges exist for current precision cancer medicine approaches during all the steps of the process, starting from clinical sampling up to bioinformatics analysis, reporting and patient treatment.

To fulfill a promise of precision oncology, appropriate bioinformatics methods for managing, integrating and analyzing large and complex data are needed. Robust, reproducible, transparent and comprehensive bioinformatics pipelines are required. Variant calling, interpretation and annotation are at the core of improving cancer treatment by providing timely and reliable therapy recommendations. Clinical reporting of molecular findings is an important step that requires close interactions between bioinformaticians and clinicians.

Part of the work of the authors of the paper has been funded by EC Horizon 2020 project No. 633974 (SOUND–Statistical multi-Omics UNDerstanding of Patient Samples), SystemsX.ch RTD Grant 2013/150, ERC Synergy Grant 609883, and Innovation Pool Funding of the University Hospital Zurich.

Reference

Singer J, Irmisch A, Ruscheweyh H-J, et al. Briefings in Bioinformatics, bbx143, Published 18 December 2017. doi: 10.1093/bib/bbx143. [Epub ahead of print]