2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Clinical utility of genomic sequencing for hereditary cancer syndromes: an observational chart review

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This study aimed to assess the diagnostic yield and management changes resulting from genomic sequencing (GS) for patients with suspected hereditary cancer syndromes (HCS). The study included 276 patients who had previously received negative genetic testing. The results showed that GS provided a modest increase in diagnostic utility (10%) compared to standard panels, but at the cost of a high frequency of variants of uncertain significance (VUS) (90%). Most positive findings from GS were in genes associated with low/moderate penetrance for cancer or carrier status for an HCS. These results highlighted the need for more evidence-based guidelines for the management of these low/moderate risk results, as management recommendations showed variations between different clinicians. The study also found that LP/P variants led to 94 recommendations in 21 patients, with the most common recommendations being genetic counseling, communication to relatives, and cascade testing. The completion rate of management recommendations made by study clinicians was 90%. However, the study also found inconsistencies in the management of certain genes between study clinicians and consulting clinicians. The findings of this study emphasize the need to build the evidence base on cancer risks for low/moderate penetrance genes and to evaluate the clinical utility and health outcomes of using GS as a first-tier test for HCS families. Further research is needed to inform best practices and develop guidelines for the use of GS in the management of hereditary cancer syndromes.

Asset Subtitle

Presenting Author - Salma A. Shickh, MSc; Co-Author - Chloe Mighton, MSc; Co-Author - Marc Clausen, MA; Co-Author - Rita Kodida, MSc, CCGC; Co-Author - Jordan Sam, MHSc; Co-Author - Daena Hirjikaka, BSc; Co-Author - Emma Reble, MSc; Co-Author - Tracy Graham, CGC; Co-Author - Seema Panchal, MSc, CGC; Co-Author - Andrea Eisen, MD; Co-Author - Christine Elser, MD; Co-Author - Kasmintan A. Schrader, MBBS, PhD, FRCPC, DABMGG; Co-Author - Nancy N Baxter, MD/PhD; Co-Author - Andreas Laupacis, MD, MSc, BA; Co-Author - Jordan Lerner-Ellis, PhD; Co-Author - Raymond H. Kim, MD; Co-Author - Yvonne Bombard, PhD;

Meta Tag

Cancer Syndromes

Counseling

Ethical Legal and Social Issues

Exome sequencing

Genetic Testing

Genome sequencing

Policy Issues

Co-Author Chloe Mighton, MSc

Co-Author Marc Clausen, MA

Co-Author Rita Kodida, MSc, CCGC

Co-Author Jordan Sam, MHSc

Co-Author Daena Hirjikaka, BSc

Co-Author Emma Reble, MSc

Co-Author Tracy Graham, CGC

Co-Author Seema Panchal, MSc, CGC

Co-Author Andrea Eisen, MD

Co-Author Christine Elser, MD

Co-Author Kasmintan A. Schrader, MBBS, PhD, FRCPC, DABMGG

Co-Author Nancy N Baxter, MD/PhD

Co-Author Andreas Laupacis, MD, MSc, BA

Co-Author Jordan Lerner-Ellis, PhD

Co-Author Raymond H. Kim, MD

Co-Author Yvonne Bombard, PhD

Presenting Author Salma A. Shickh, MSc

Keywords

genomic sequencing

diagnostic yield

hereditary cancer syndromes

variants of uncertain significance

low/moderate penetrance

evidence-based guidelines

genetic counseling

cascade testing

completion rate

cancer risks