Occurrence of variants of unknown clinical significance in genetic testing for hereditary breast and ovarian cancer syndrome and Lynch syndrome: a literature review and analytical observational retrospective cohort study

BMC Medical Genomics

Research

Amina Scherz¹  Manuela Rabaglio¹  Muriel Fluri¹  Felicia Adam² 

[1] Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland;Medical Faculty of the University of Bern, Bern, Switzerland;

关键词: Hereditary breast and ovarian cancer;    Lynch syndrome;    VUS;    BRCA1;    BRCA2;    MMR genes;    Multigene panel;   

DOI  :  10.1186/s12920-023-01437-7

 received in 2022-07-25, accepted in 2023-01-09,  发布年份 2023

来源: Springer

【 摘 要 】

Background and purposeOver the last decade, the implementation of multigene panels for hereditary tumor syndrome has increased at our institution (Inselspital, University Hospital Berne, Switzerland). The aim of this study was to determine the prevalence of variants of unknown significance (VUS) in patients with suspected Lynch syndrome and suspected hereditary breast and ovarian cancer syndrome, the latter in connection with the trend toward ordering larger gene panels.ResultsRetrospectively collected data from 1057 patients at our institution showed at least one VUS in 126 different cases (11.9%). In patients undergoing genetic testing for BRCA1/2, the prevalence of VUS was 6%. When < 10 additional genes were tested in addition to BRCA1/2, the prevalence increased to 13.8%, and 31.8% for > 10 additional genes, respectively. The gene most frequently affected with a VUS was ATM. 6% of our patients who were tested for Lynch syndrome had a VUS result in either MLH1, MSH2 or MSH6.ConclusionsOur data demonstrate that panel testing statistically significantly increases VUS rates due to variants in non-BRCA genes. Good genetic counseling before and after obtaining results is therefore particularly important when conducting multigene panels to minimize patient uncertainty due to VUS results.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

41116_2022_35_Article_IEq187.gif

Fig. 44

41116_2022_35_Article_IEq185.gif

41116_2022_35_Article_IEq182.gif

Fig. 4