Background: Hereditary breast and ovarian cancer (HBOC) syndrome is an autosomal dominant inherited disorder that include 5–7% of all breast cancer (BC) cases and 10-15% of all ovarian cancer (OC) cases. BRCA1 and BRCA2 are the most common genes associated to HBOC syndrome. However, hereditary syndrome could be associated with germline PVs in several high- and moderate-risk genes. In recent years, Next-Generation Sequencing (NGS) has allowed to study multiple genes simultaneously, to reduce analysis costs, to led to an explosion of genetic data, and to offer more information to patients. Methods: We retrospectively collected and analyzed to BRCA1/2 test 876 patients affected by BC and OC (531 of BC, 345 of OC) among January 2016 to August 2020. Successively, we analyzed 192 patients resulted BRCA1/2 negative with a strong personal and/or family history to BC and/or OC by using Multi-gene panel testing. We evaluated 22 genes involved in risk of hereditary breast, ovarian and colorectal cancer, and other inherited tumor syndromes. Results: Analysis conducted with multi-gene panel testing revealed that 28 (14.6%) BC and OC patients showed PVs/LPVs in genes no-BRCA. In particular, we analyzed 165 BC patients and 27 OC patients, and we obtained 27 and 4 patients with PVs/LPVs in genes no-BRCA respectively. BC patients with alteration in gene over BRCA hardly showed TNBC than patients with BRCA1/2 or all wt. Moreover, among BC patients with genes altered beyond BRCA the 45.8% showed a Bilateral Breast Cancer. In OC group we observed that 75% of patients with PVs/LPVs in genes over BRCA showed a previously personal history of BC or other cancer. Conclusion: Our analysis showed that the 14.6% of patients BRCA-negative with a strong personal and/or family history to BC and/or OC presented alteration in genes beyond BRCA1/2. This result highlighted the importance of multi-gene panel testing which should be extended at all these patients and be included in clinical practice

(2021). Multigene panel testing in Hereditary Breast and Ovarian Cancer: an effective liquid biopsy approach to identify mutations in genes involved in the Homologous Recombination pathway.

Multigene panel testing in Hereditary Breast and Ovarian Cancer: an effective liquid biopsy approach to identify mutations in genes involved in the Homologous Recombination pathway

BONO, Marco
2021-01-01

Abstract

Background: Hereditary breast and ovarian cancer (HBOC) syndrome is an autosomal dominant inherited disorder that include 5–7% of all breast cancer (BC) cases and 10-15% of all ovarian cancer (OC) cases. BRCA1 and BRCA2 are the most common genes associated to HBOC syndrome. However, hereditary syndrome could be associated with germline PVs in several high- and moderate-risk genes. In recent years, Next-Generation Sequencing (NGS) has allowed to study multiple genes simultaneously, to reduce analysis costs, to led to an explosion of genetic data, and to offer more information to patients. Methods: We retrospectively collected and analyzed to BRCA1/2 test 876 patients affected by BC and OC (531 of BC, 345 of OC) among January 2016 to August 2020. Successively, we analyzed 192 patients resulted BRCA1/2 negative with a strong personal and/or family history to BC and/or OC by using Multi-gene panel testing. We evaluated 22 genes involved in risk of hereditary breast, ovarian and colorectal cancer, and other inherited tumor syndromes. Results: Analysis conducted with multi-gene panel testing revealed that 28 (14.6%) BC and OC patients showed PVs/LPVs in genes no-BRCA. In particular, we analyzed 165 BC patients and 27 OC patients, and we obtained 27 and 4 patients with PVs/LPVs in genes no-BRCA respectively. BC patients with alteration in gene over BRCA hardly showed TNBC than patients with BRCA1/2 or all wt. Moreover, among BC patients with genes altered beyond BRCA the 45.8% showed a Bilateral Breast Cancer. In OC group we observed that 75% of patients with PVs/LPVs in genes over BRCA showed a previously personal history of BC or other cancer. Conclusion: Our analysis showed that the 14.6% of patients BRCA-negative with a strong personal and/or family history to BC and/or OC presented alteration in genes beyond BRCA1/2. This result highlighted the importance of multi-gene panel testing which should be extended at all these patients and be included in clinical practice
2021
Breast, Ovarian, Cancer, Multigene panel, Homologous Recombination
(2021). Multigene panel testing in Hereditary Breast and Ovarian Cancer: an effective liquid biopsy approach to identify mutations in genes involved in the Homologous Recombination pathway.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/479959
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