title: Panel-based testing for inherited colorectal cancer: a descriptive study of clinical testing performed by a US laboratory.
abstract: 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.
authors: H. Lee Moffitt Cancer Center, Tampa, FL, USA.
authors: D
authors: D
authors: Cragun
authors: C
authors: C
authors: Radford
authors: J S
authors: JS
authors: Dolinsky
authors: M
authors: M
authors: Caldwell
authors: E
authors: E
authors: Chao
authors: T
authors: T
authors: Pal
mesh_terms: D064447:Checkpoint Kinase 2 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D045647:DNA Glycosylases / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009154:Mutation; D014481:United States
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase
keywords: ColoNext; clinical genetics; hereditary cancer syndromes; multiplex genetic testing; next generation sequencing; variants of unknown significance