Abstract
Background
Breast cancer is the most common malignancy in women and thought to be hereditary
in 10% of patients. Recent next-generation sequencing studies have increased the detection
of pathogenic or likely pathogenic (P/LP) variants in genes other than BRCA1/2 in patients with breast cancer. This study evaluated pathogenic variants, likely
pathogenic variants, and variants of unknown significance in 18 hereditary cancer
susceptibility genes in patients with BRCA1/2-negative breast cancer.
Patients and Methods
This retrospective study included 188 high-risk BRCA1/2-negative patients with breast cancer tested with a multigene cancer panel using next-generation
sequencing.
Results
Among 188 proband cases, 18 variants in 21 patients (11.1%) were classified as P/LP
in PALB2 (n = 6), CHEK2 (n = 5), MUTYH (n = 4), ATM (n = 3), TP53 (n = 2), BRIP1 (n = 1), and MSH2 (n = 1). Three novel P/LP variants were identified. An additional 28 variants were classified
as variants of unknown significance and detected in 30 different patients (15.9%).
Conclusion
This is one of the largest study from Turkey to investigate the mutation spectrum
in non-BRCA hereditary breast cancer susceptibility genes. A multigene panel test
increased the likelihood of identifying a molecular diagnosis in patients with BRCA
1/2-negative breast cancer at risk for a hereditary breast cancer syndrome. More studies
are needed to enable the clinical interpretation of these P/LP variants in hereditary
patients with breast cancer.
Keywords
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Article Info
Publication History
Published online: April 12, 2021
Accepted:
April 5,
2021
Received in revised form:
February 19,
2021
Received:
June 24,
2020
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
