机构：[1]Research Center,Fourth Hospital of Hebei Medical University, Shijiazhuang, China河北医科大学第四医院[2]Breast Cancer Center,Fourth Hospital of Hebei Medical University, Shijiazhuang, China河北医科大学第四医院[3]Medical Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, China河北医科大学第四医院
Background: In locally advanced triple-negative breast cancer (TNBC), patients who did not achieve pathologic complete response (non-pCR) after neoadjuvant chemotherapy develop rapid tumor metastasis. Tumor mutation burden (TMB) is a potential biomarker of cancer therapy, though whether it is applicable to TNBC is still unclear. Methods: A total of 14 non-pCR TNBC patients were enrolled, and tissue samples from radical operation were collected. Of these, 7 cases developed disease progression within 12 months after operation [short disease-free survival (short DFS)], while others showed longer DFS over 1 year (long DFS). Next generation sequencing (NGS) analysis targeting 422 cancer-related genes and in vitro studies were performed. Results: A total of 72 mutations were detected within 14 patients, which ranged from 1 to 8 per patient with a median mutations number of 5. The median number of mutations in the short-DFS group was higher than that in the long-DFS group (6.0 vs. 4.3; P=0.094). Furthermore, 6 gene mutation types were detected, with missense mutations displayed in the majority (36/72, 50.0%). No correlation between mutation type and DFS was found. Among 422 cancer-related genes, alterations in 30 genes were detected. TP53 (12/14, 85.7%) was the most common mutation gene in the entire cohort. RB1 mutations significantly occurred in patients with high Ki-67 scores (P=0.013). Additionally, 4 mutations of PTPN13 (57.1%, 4/7) and 3 of JARID2 (42.9%, 3/7) were only detected in the short-DFS group, while patients with JARID2 mutation had a significantly shorter DFS period (P=0.026). Experiments in vitro confirmed that JARID2 gene was widely expressed in various breast cancer cell lines. Knockdown of JARID2 in MD-MBA-231 cells by small interfering RNA (siRNA) decreased the expression of E-cadherin, and increased the levels of vimentin, MMP7, and MMP9. Conclusions: In non-pCR TNBC, JARID2 mutation and TMB elevated in patients with short-DFS, indicating the potential prognostic biomarkers and therapeutic molecular targets for locally advanced TNBC.
基金：
This work was supported by the China Anti-Cancer Association Research Grant.
第一作者机构：[1]Research Center,Fourth Hospital of Hebei Medical University, Shijiazhuang, China
共同第一作者：
通讯作者：
通讯机构：[1]Research Center,Fourth Hospital of Hebei Medical University, Shijiazhuang, China[2]Breast Cancer Center,Fourth Hospital of Hebei Medical University, Shijiazhuang, China[*1]Breast Cancer Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.[*2]Research Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
推荐引用方式(GB/T 7714)：
Zhang Xiangmei,Li Jingping,Yang Qing,et al.Tumor mutation burden and JARID2 gene alteration are associated with short disease-free survival in locally advanced triple-negative breast cancer[J].ANNALS OF TRANSLATIONAL MEDICINE.2020,8(17):doi:10.21037/atm-20-3773.
APA：
Zhang, Xiangmei,Li, Jingping,Yang, Qing,Wang, Yanfang,Li, Xinhui...&Shan, Baoen.(2020).Tumor mutation burden and JARID2 gene alteration are associated with short disease-free survival in locally advanced triple-negative breast cancer.ANNALS OF TRANSLATIONAL MEDICINE,8,(17)
MLA：
Zhang, Xiangmei,et al."Tumor mutation burden and JARID2 gene alteration are associated with short disease-free survival in locally advanced triple-negative breast cancer".ANNALS OF TRANSLATIONAL MEDICINE 8..17(2020)
：