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. 2021 Aug;6(4):100235.
doi: 10.1016/j.esmoop.2021.100235. Epub 2021 Aug 7.

Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge

M Bono  1 , D Fanale  1 , L Incorvaia  2 , D Cancelliere  1 , A Fiorino  1 , V Calò  1 , A Dimino  1 , C Filorizzo  1 , L R Corsini  1 , C Brando  1 , G Madonia  1 , A Cucinella  1 , R Scalia  1 , N Barraco  1 , F Guadagni  3 , E Pedone  1 , G Badalamenti  1 , A Russo  4 , V Bazan  2
Affiliations

Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge

M Bono et al. ESMO Open. 2021 Aug.

Abstract

Background: Hereditary breast cancer (BC), ovarian cancer (OC), and pancreatic cancer (PC) are the major BRCA-associated tumours. However, some BRCA1/2-wild-type (wt) patients with a strong personal and/or family history of cancer need a further genetic testing through a multi-gene panel containing other high- and moderate-risk susceptibility genes.

Patients and methods: Our study was aimed to assess if some BC, OC, or PC patients should be offered multi-gene panel testing, based on well-defined criteria concerning their personal and/or family history of cancer, such as earliness of cancer onset, occurrence of multiple tumours, or presence of at least two or more affected first-degree relatives. For this purpose, 205 out of 915 BC, OC, or PC patients, resulted negative for BRCA1/2 and with significant personal and/or family history of cancer, were genetically tested for germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes different from BRCA1/2.

Results: Our investigation revealed that 31 (15.1%) out of 205 patients harboured germline PVs/LPVs in no-BRCA genes, including PALB2, CHEK2, ATM, MUTYH, MSH2, and RAD51C. Interestingly, in the absence of an analysis conducted through multi-gene panel, a considerable percentage (15.1%) of PVs/LPVs would have been lost.

Conclusions: Providing a multi-gene panel testing to BRCA1/2-wt BC/OC/PC patients with a strong personal and/or family history of cancer could significantly increase the detection rates of germline PVs/LPVs in other cancer predisposition genes beyond BRCA1/2. The use of a multi-gene panel testing could improve the inherited cancer risk estimation and clinical management of patients and unaffected family members.

Keywords: breast cancer; germline pathogenic variants; multi-gene panel testing; ovarian cancer; pancreatic cancer.

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Conflict of interest statement

Disclosure The authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
Distribution of PVs/LPVs detected in 31 BC, OC, or PC patients analysed with multi-gene panel testing. The OncoPrint, showing the identified PVs/LPVs by heatmap, was obtained by the informatics tool Mutation Mapper (cBioPortal for Cancer Genomics). The intronic variant sequences (IVS) are not shown. BC, breast cancer; LPV, likely pathogenic variant; OC, ovarian cancer; PC, pancreatic cancer; PV, pathogenic variant.
Figure 2
Figure 2
Percentage distribution of no-BRCA genes altered in BC, OC, or PC patients detected by multi-gene panel testing. BC, breast cancer; OC, ovarian cancer; PC, pancreatic cancer.
See this image and copyright information in PMC

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