Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic.

摘要: Despite the potential of whole-genome sequencing (WGS) to improve patient diagnosis and care, empirical value WGS in cancer genetics clinic is unknown. We performed on members two cohorts patients: those with BRCA1/2 mutations (n = 176) without (n = 82). Initial analysis potentially pathogenic variants (PPVs, defined as nonsynonymous allele frequency < 1% ESP6500) 163 clinically-relevant genes suggested that will provide useful clinical results. This despite fact a majority PPVs were novel missense likely be classified unknown significance (VUS). Furthermore, previously reported did not always associate their predicted diseases our patients. suggests use require large-scale efforts consolidate data accuracy interpretation rare variants. While loss-of-function (LoF) represented only small fraction PPVs, identified additional risk LoF patients known led diagnoses 21% non-BRCA after expanding 3209 ClinVar genes. These illustrate how can used ability discover patients' genetic risks.