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.

Adam, Felicia; Fluri, Muriel; Scherz, Amina; Rabaglio, Manuela (2023). 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, 16(1), p. 7. BioMed Central 10.1186/s12920-023-01437-7

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BACKGROUND AND PURPOSE

Over 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.

RESULTS

Retrospectively 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.

CONCLUSIONS

Our 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Scherz, Amina, Rabaglio, Manuela Elena

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1755-8794

Publisher:

BioMed Central

Language:

English

Submitter:

Pubmed Import

Date Deposited:

25 Jan 2023 15:44

Last Modified:

05 Feb 2023 02:25

Publisher DOI:

10.1186/s12920-023-01437-7

PubMed ID:

36647026

Uncontrolled Keywords:

BRCA1 BRCA2 Hereditary breast and ovarian cancer Lynch syndrome MMR genes Multigene panel VUS

BORIS DOI:

10.48350/177506

URI:

https://boris.unibe.ch/id/eprint/177506

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