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Breast Cancer
Published in: Breast Cancer 6/2021

01-11-2021 | Original Article

Follow-up of tissue genomics in BRCA1/2 carriers who underwent prophylactic surgeries

Authors: Vassiliki Kotoula, Kyriaki Papadopoulou, Ioannis Tikas, Florentia Fostira, Eleni Vrettou, Sofia Chrisafi, Elena Fountzilas, Georgia-Angeliki Koliou, Paraskevi Apostolou, Konstantinos Papazisis, Thomas Zaramboukas, Anthoula Asimaki-Vlachopoulou, Spyros Miliaras, Ananias Ananiadis, Christos Poulios, Ioannis Natsiopoulos, Aris Tsiftsoglou, Efterpi Demiri, George Fountzilas

Published in: Breast Cancer | Issue 6/2021

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Abstract

Purpose

The genomic status of non-malignant tissues from carriers of pathogenic germline BRCA1/2 (gBRCA1/2) variants may reveal information towards individualized prophylaxis. We performed spatiotemporal tissue genotype comparisons in a real-life cohort of gBRCA1/2 carriers of Greek origin, who underwent multiple risk-reducing/prophylactic surgeries at various time points.

Methods

Fifty-three women (median age 36 years) within cancer families were observed for up to 37.5 years; 43 were cancer carriers and 10 were healthy carriers. Histology review and genotyping were performed for 187 paraffin tissues (average: 3.5 per carrier) including 46 carcinomas (40 breast) and 141 non-malignant breast and gynecological samples.

Results

High allelic imbalance (AI) and somatic pathogenic TP53 variants were present in cancer carriers only (p values < 0.0001). High AI was associated with gBRCA1/2 indels (p < 0.0001) and gBRCA2 alterations (p = 0.0109). Somatic (pathogenic) variants were infrequently shared between non-malignant tissues and matched carcinomas. Aberrations of gBRCA1 variant heterozygosity were noticed in tissues from cancer carriers only (13/43, 30.2%). These pertained to classic LOH (neoplastic lesions in 9/43 carriers, 20.9%) and under-representation of the germline variants (5 samples, 4 non-malignant, all in the breast). Both aberrations coexisted in matched samples in one case. Over time, germline variant heterozygosity prevailed in non-malignant tissues; intra-carrier genomic alterations were aggravated (21.1%), ameliorated (26.3%) or remained stable.

Conclusion

This real-life case study supports the need to address tissue genotypes from prophylactic surgeries in combination with polygenic scores towards personalized prophylaxis. To this end, knowing the traditionally classified pathogenic potential of a gBRCA1/2 variant may not be enough.
Appendix
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Metadata
Title
Follow-up of tissue genomics in BRCA1/2 carriers who underwent prophylactic surgeries
Authors
Vassiliki Kotoula
Kyriaki Papadopoulou
Ioannis Tikas
Florentia Fostira
Eleni Vrettou
Sofia Chrisafi
Elena Fountzilas
Georgia-Angeliki Koliou
Paraskevi Apostolou
Konstantinos Papazisis
Thomas Zaramboukas
Anthoula Asimaki-Vlachopoulou
Spyros Miliaras
Ananias Ananiadis
Christos Poulios
Ioannis Natsiopoulos
Aris Tsiftsoglou
Efterpi Demiri
George Fountzilas
Publication date
01-11-2021
Publisher
Springer Singapore
Published in
Breast Cancer / Issue 6/2021
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-021-01276-3

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