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Journal of Cancer Research and Clinical Oncology

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10.10.2018 | Original Article – Clinical Oncology

Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings

verfasst von: Sandra Bonache, Irene Esteban, Alejandro Moles-Fernández, Anna Tenés, Laura Duran-Lozano, Gemma Montalban, Vanessa Bach, Estela Carrasco, Neus Gadea, Adrià López-Fernández, Sara Torres-Esquius, Francesco Mancuso, Ginevra Caratú, Ana Vivancos, Noemí Tuset, Judith Balmaña, Sara Gutiérrez-Enríquez, Orland Diez

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 12/2018

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Abstract

Purpose

Few and small studies have been reported about multigene testing usage by massively parallel sequencing in European cancer families. There is an open debate about what genes should be tested, and the actionability of some included genes is under research.

Methods

We investigated a panel of 34 known high/moderate-risk cancer genes, including 16 related to breast or ovarian cancer (BC/OC) genes, and 63 candidate genes to BC/OC in 192 clinically suspicious of hereditary breast/ovarian cancer (HBOC) Spanish families without pathogenic variants in BRCA1 or BRCA2 (BRCA1/2).

Results

We identified 16 patients who carried a high- or moderate-risk pathogenic variant in eight genes: 4 PALB2, 3 ATM, 2 RAD51D, 2 TP53, 2 APC, 1 BRIP1, 1 PTEN and 1 PMS2. These findings led to increased surveillance or prevention options in 12 patients and predictive testing in their family members. We detected 383 unique variants of uncertain significance in known cancer genes, of which 35 were prioritized in silico. Eighteen loss-of-function variants were detected in candidate BC/OC genes in 17 patients (1 BARD1, 1 ERCC3, 1 ERCC5, 2 FANCE, 1 FANCI, 2 FANCL, 1 FANCM, 1 MCPH1, 1 PPM1D, 2 RBBP8, 3 RECQL4 and 1 with SLX4 and XRCC2), three of which also carry pathogenic variants in known cancer genes.

Conclusions

Eight percent of the BRCA1/2 negative patients carry pathogenic variants in other actionable genes. The multigene panel usage improves the diagnostic yield in HBOC testing and it is an effective tool to identify potentially new candidate genes.

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Titel: Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings
verfasst von: Sandra Bonache
Irene Esteban
Alejandro Moles-Fernández
Anna Tenés
Laura Duran-Lozano
Gemma Montalban
Vanessa Bach
Estela Carrasco
Neus Gadea
Adrià López-Fernández
Sara Torres-Esquius
Francesco Mancuso
Ginevra Caratú
Ana Vivancos
Noemí Tuset
Judith Balmaña
Sara Gutiérrez-Enríquez
Orland Diez
Publikationsdatum: 10.10.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 12/2018
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-018-2763-9

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Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings

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Purpose

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Results

Conclusions

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