期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-09255-1
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资金
- National Natural Science Foundation of China [81330063, 81672768, 81702449, 81773150, 81490753, 81830086]
- National Key Research and Development Program of China [2016YFC1302100]
- fund of Sanming Project of Medicine in Shenzhen [SZSM201812088]
- Key Research and Development Program of Shanxi Province [201603D321048]
- Scientific Research Foundation of the Shanxi Province for Returned Scholars [2015-key3, 2017-064]
- Foundation for Youths of Shanxi Province [201701D221250]
- Key Innovative Team in Science & Technology of Shanxi Province [201605D131045-16]
- Key Laboratory of Shanxi Province [201705D111003]
- Fund for Shanxi 1331 Project and 1331 Project Key Subjects Construction
- Program for the OIT of Higher Learning Institutions of Shanxi
- Fund for Shanxi Key Subjects Construction
- funding for Sanjin Scholars
Esophageal squamous cell carcinoma (ESCC) ranks fourth among cancer-related deaths in China due to the lack of actionable molecules. We performed whole-exome and T-cell receptor (TCR) repertoire sequencing on multi-regional tumors, normal tissues and blood samples from 39 ESCC patients. The data revealed 12.8% of ERBB4 mutations at patient level and functional study supported its oncogenic role. 18% of patients with early BRCA1/2 variants were associated with high-level contribution of signature 3, which was validated in an independent large cohort (n = 508). Furthermore, knockdown of BRCA1/2 dramatically increased sensitivity to cisplatin in ESCC cells. 5% of patients harbored focal high-level amplification of CD274 that led to massive expression of PD-L1, and might be more sensitive to immune checkpoint blockade. Finally, we found a tight correlation between genomic and TCR repertoire intra-tumor heterogeneity (ITH). Collectively, we reveal high-level ITH in ESCC, identify several potential actionable targets and may provide novel insight into ESCC treatment.
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