High-speed and low-cost sequencing, combined with intense clinical interest, have led to widespread use of multi-gene testing for inherited variants conferring risk of cancer. Millions of genetic tests for inherited risk of cancer have been administered since commercial testing of BRCA1/2 variants began in 1996, and yet new variants continue to be found. Determining a variant’s clinical significance can be a challenge.

As hereditary cancer testing panels have transitioned to sequencing dozens of genes, rather than only expressed segments of BRCA1/2, the information needed to advance biomedical research and to determine the clinical significance of cancer-gene variants vastly exceeds the capacity of any one lab or institution.

Interpretation of inherited cancer-gene variants depends on sharing information, that is, on a well-functioning knowledge commons. A commons of sorts is already forming, but it is fragile and may not be sustainable. It will still be forming while this project unfolds; indeed the cancer genomic variant commons will be evolving for decades. Yet fateful decisions are being made in the early creation phase, framing the range of future choices. We intend to study this process and give feedback to those making crucial decisions to improve the effectiveness of the cancer genomic variant commons. We intend to provide foresight to those building the commons we will live with for decades.

The Sulston Project is supported by a grant from the US National Cancer Institute: R01 CA237118, April 2019-March 2023.