Panel-based testing for inherited colorectal cancer: a descriptive study of clinical testing performed by a US laboratory

摘要

Next-generation sequencing enables testing for multiple genes simultaneously (‘panel-based testing’) as opposed to sequential testing for one inherited condition at a time (‘syndrome-based testing’). This study presents results from patients who underwent hereditary colorectal cancer (CRC) panel-based testing (‘ColoNext™’). De-identified data from a clinical testing laboratory were used to calculate (1) frequencies for patient demographic, clinical, and family history variables and (2) rates of pathogenic mutations and variants of uncertain significance (VUS). The proportion of individuals with a pathogenic mutation who met national syndrome-based testing criteria was also determined. Of 586 patients, a pathogenic mutation was identified in 10.4%, while 20.1% had at least one VUS. After removing eight patients with CHEK2 mutations and 11 MUTYH heterozygotes, the percentage of patients with ‘actionable’ mutations that would clearly alter cancer screening recommendations per national guidelines decreased to 7.2%. Of 42 patients with an ‘actionable’ result, 30 (71%) clearly met established syndrome-based testing guidelines. This descriptive study is among the first to report on a large clinical series of patients undergoing panel-based testing for inherited CRC. Results are discussed in the context of benefits and concerns that have been raised about panel-based testing implementation.Conflict of interestCristi Radford and Jill Dolinsky are full-time employees for the commercial laboratory Ambry Genetics, which performs ColoNext™ testing. Elizabeth Chao is a paid consultant for Ambry. Deborah Cragun, Meghan Caldwell, and Tuya Pal report no potential conflicts of interest. Specifically, they are not employed by Ambry, and they did not receive any financial or other incentives from Ambry.