Second generation sequencing detection breast cancer susceptibility gene variants for risk prediction and clinical treatment
10.3969/j.issn.1000-8179.2017.20.203
- VernacularTitle:二代测序检测乳腺癌易感基因在乳腺癌发病风险预测及临床治疗中的应用
- Author:
WU NAN
1
;
YU JINPU
;
ZHAO JING
;
ZHAO YANG
;
MU KUN
;
ZHANG JUN
;
JIN ZHAO
;
LIU JUNTIAN
Author Information
1. 天津医科大学肿瘤医院乳腺二科
- Keywords:
second generation sequencing;
breast cancer susceptibility gene;
risk prediction;
clinical intervention;
prognosis evaluation
- From:
Chinese Journal of Clinical Oncology
2017;44(20):1024-1028
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the function of breast cancer susceptibility gene variants in predicting breast cancer risk and guid-ing clinical treatment through DNA sequencing. Methods:This study involved 146 patients, 71 high-risk cases, and 55 healthy people, totaling 272 cases. The subjects were treated in Tianjin Medical University Cancer Institute and Hospital from November 2013 to July 2015. Genomic DNA was sequenced by a second generation sequencing platform. All exon areas of six common breast cancer suscepti-bility genes (BRCA1, BRCA2, PTEN, STK11, TP53, and RAP1) were sequenced through amplicon sequencing method. Meaningful vari-ants including single nucleotide variants (SNVs), insertion-deletions (InDels) and nonsense mutations were selected and statistical methods, such as t test andχ2 test, were used to analyze the statistical differences in incidence rates among three groups. Results:A total of 177 meaningful variants were confirmed, including 50 SNVs, 8 nonsense mutations, and 9 InDels. Among the variants, 31 were recorded in the Exome Aggregation Consortium (ExAC), 40 were noted in ClinVar database, and 21 were not encoded in the present da-tabase, which were defined as new variants in this study. Conversely, 57 variants (85.1%) were found in breast cancer patients and high-risk cases, and the incidence of axillary lymph node metastasis (P=0.010) and pathological stages (P=0.002) in mutation positive patients were both higher than mutation negative patients. Moreover, the percentage of family history of cancer (P=0.005) and triple negative breast cancer (P=0.009) were both higher in patients carrying pathogenic mutations than in nonpathogenic patients. Conclu-sion:Breast cancer susceptibility gene variants may not only be a tool used to predict the risk of getting breast cancer but also a mean-ingful guideline for the clinical treatment and prognosis evaluation.
