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. 2020 Aug 15:2020:6739823.
doi: 10.1155/2020/6739823. eCollection 2020.

Identification of Recurrent Variants in BRCA1 and BRCA2 across Multiple Cancers in the Chinese Population

Yue Jiang  1   2   3 , Ting Tian  1   2   3 , Chengxiao Yu  1   2   3 , Wen Zhou  1   2   3 , Junzhe Yang  4 , Yifeng Wang  1   2   3 , Yang Wen  1   2   3 , Jiaping Chen  1   2   3 , Juncheng Dai  1   2   3 , Guangfu Jin  1   2   3 , Hongxia Ma  1   2   3 , Hongbing Shen  1   2   3 , Zhibin Hu  1   2   3
Affiliations

Identification of Recurrent Variants in BRCA1 and BRCA2 across Multiple Cancers in the Chinese Population

Yue Jiang et al. Biomed Res Int. .

Abstract

BRCA1 and BRCA2 as important DNA repair genes have been thoroughly investigated in abundant studies. The potential relationships of BRCA1/2 pathogenic variants between multicancers have been verified in Caucasians but few in Chinese. In this study, we performed a two-stage study to screen BRCA1/2 pathogenic variants or variants of uncertain significance (VUS) with 7580 cancer cases and 4874 cancer-free controls, consisting of a discovery stage with 70 familial breast cancer cases and a subsequent validation stage with 7510 cases (3217 breast cancer, 1133 cervical cancer, 2044 hepatocellular carcinoma, and 1116 colorectal cancer). 48 variants were obtained from 70 familial breast cancer cases after BRCA1/2 exon detection, and finally, 20 pathogenic variants or VUS were selected for subsequent validation. Four recurrent variants in sporadic cases (BRCA1 c.4801A>T, BRCA1 c.3257del, BRCA1 c.440del, and BRCA2 c.7409dup) were identified and three of them were labeled Class 5 by ENIGMA. Two variants (BRCA1 c.3257del and c.440del) were specific in breast cancer cases, while BRCA2 c.7409dup and c.4307T>C were detected in two hepatocellular carcinoma patients and the BRCA1 c.4801A>T variant in one cervical cancer patient, respectively. Moreover, BRCA1 c.3257del was the most frequent variant observed in Chinese sporadic breast cancer and showed increased proliferation of BRCA1 c.3257del-overexpressing triple-negative breast cancer cell lines (MDA-MB-231) in vitro. In addition to the known founder deleterious mutations, our findings highlight that the recurrently pathogenic variants in breast cancer cases could be taken as candidate genetic screening loci for a more efficient genetic screening of the Chinese population.

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Conflict of interest statement

All authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of BRCA1 and BRCA2 germline variant selection.
Figure 2
Figure 2
Recurrent pathogenic variants detected in the validation stage on exons of (a) BRCA1 and (b) BRCA2. Exons are colored in blue; circles represent validated cases that are colored in red (breast cancer), green (cervical cancer), and gray (hepatocellular carcinoma).
Figure 3
Figure 3
(a) The BRCA1 mRNA level of MDA-MB-231 transfected with BRCA1c.3257del plasmids was significantly reduced (P < 0.05) compared to those transfected with wild-type BRCA1 plasmids. Western blot analysis showed that the BRCA1 protein level translated by BRCA1c.3257del-overexpressed cells was lower than BRCA1WT in MDA-MB-231 cells. (b) The colony formation efficiency of MDA-MB-231 cells transfected with BRCA1c.3257del was significantly increased (P < 0.05). (c) Cell proliferation of BRCA1c.3257del (red) and BRCA1WT (blue) was measured using the CCK-8 assay. Increased proliferation of BRCA1c.3257del-overexpressing MDA-MB-231 cells was detected in vitro (P < 0.05).
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References

    1. Siegel R. L., Miller K. D., Jemal A. Cancer statistics, 2018. CA: A Cancer Journal for Clinicians. 2018;68(1):7–30. doi: 10.3322/caac.21442. - DOI - PubMed
    1. Claus E. B., Schildkraut J. M., Thompson W. D., Risch N. J. The genetic attributable risk of breast and ovarian cancer. Cancer. 1996;77(11):2318–2324. doi: 10.1002/(SICI)1097-0142(19960601)77:11<2318::AID-CNCR21>3.0.CO;2-Z. - DOI - PubMed
    1. Kurian A. W., Hare E. E., Mills M. A., et al. Clinical evaluation of a multiple-gene sequencing panel for hereditary cancer risk assessment. Journal of Clinical Oncology. 2014;32(19):2001–2009. doi: 10.1200/JCO.2013.53.6607. - DOI - PMC - PubMed
    1. Miki Y., Swensen J., Shattuck-Eidens D., et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266(5182):66–71. doi: 10.1126/science.7545954. - DOI - PubMed
    1. Wooster R., Bignell G., Lancaster J., et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378(6559):789–792. doi: 10.1038/378789a0. - DOI - PubMed

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