UNASSIGNED: 7 Background: Multiple-gene sequencing panels are entering clinical practice. We report on research testing with a custom sequencing panel comprising 43 genes and 32 @entity5 -associated variants among @entity1 referred for assessment of @entity5344 risk. METHODS: @entity1 referred to the Stanford Cancer Genetics Program for clinical @entity5345 and @entity2674 ( @entity14049 ) mutation testing from 2002-2012 were invited to donate a blood sample for research on an Institutional Review Board-approved protocol. Blood samples were frozen at -80 degrees, and DNA extracted after <1-10 years. The entire coding region, exon-intron boundaries (+/- 10bp) and all known pathogenic variants in other regions were sequenced for 43 genes that have published associations with risk of @entity5344 . An additional 32 @entity5 -associated variants were also sequenced. Clinically significant results were disclosed to @entity1 . RESULTS: Germline DNA samples were sequenced from 199 @entity1 : 141 had @entity0 , and 57 carried known @entity14049 mutations. Analytic results for @entity14049 sequencing and pathogenicity interpretations were concordant with prior clinical testing for all @entity1 . Twenty variants designated as pathogenic, either based on published literature or due to a novel truncating or splice donor/acceptor effect, were observed in genes other than @entity14049 , including ATM, @entity60048 , @entity5962 , @entity986 , @entity20701 , @entity6756 , @entity9485 , @entity20618 , and @entity38981 . Thirteen @entity1 had pathogenic variants warranting a change in @entity5 screening or risk reduction based on practice guidelines; they were invited for confirmatory clinical testing and counseling. One 53-year old @entity1 with a personal history of @entity0 was found to carry a pathogenic @entity6756 mutation; she underwent risk-reducing salpingo-oophorectomy and colonoscopy, with removal of a @entity652 . CONCLUSIONS: Among @entity1 referred for @entity14049 mutation testing, a comprehensive sequencing assay identified 20 [10.1%, 95% confidence interval (CI) 6.5%-15.1%] pathogenic mutations in other genes, of which 13 (6.5%, CI 3.8%-11%) prompted a change in care. Disclosure of research results to @entity1 was feasible and well-tolerated.

Evaluation of a XXXX gene sequencing panel in a hereditary risk assessment clinic.

@entity1 :: ('9606', 'Species') :: ['patient', 'women', 'Patients', 'participants', 'patients'] @entity6756 :: ('4292', 'Gene') :: ['MLH1'] @entity5344 :: ('MESH:D061325', 'Disease') :: ['hereditary breast and ovarian cancer', 'breast, ovarian and other cancers'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast and endometrial cancers', 'breast cancer'] @entity986 :: ('1029', 'Gene') :: ['CDKN2A'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity5345 :: ('672', 'Gene') :: ['BRCA1'] @entity2674 :: ('675', 'Gene') :: ['BRCA2'] @entity5962 :: ('999', 'Gene') :: ['CDH1'] @entity20701 :: ('4595', 'Gene') :: ['MUTYH'] @entity14049 :: ('675;672', 'Gene') :: ['BRCA1/2'] @entity38981 :: ('84464', 'Gene') :: ['SLX4'] @entity9485 :: ('4683', 'Gene') :: ['NBN'] @entity652 :: ('MESH:D000236', 'Disease') :: ['tubular adenoma'] @entity20618 :: ('5644', 'Gene') :: ['PRSS1'] @entity60048 :: ('641', 'Gene') :: ['BLM']
@entity5 :: (MESH:D009369,Disease) :: ['cancer']
