Lung squamous cell carcinoma （LUSC） causes approximately 400 000 deaths each year worldwide. The occurrence of LUSC is attributed to exposure to cigarette smoke, which induces the development of numerous genomic abn...Lung squamous cell carcinoma （LUSC） causes approximately 400 000 deaths each year worldwide. The occurrence of LUSC is attributed to exposure to cigarette smoke, which induces the development of numerous genomic abnormalities. However, few studies have investigated the genomic variations that occur only in normal tissues that have been similarly exposed to tobacco smoke as tumor tissues. In this study, we sequenced the whole genomes of three normal lung tissue samples and their paired adjacent squamous cell carcinomas. We then called genomic variations specific to the normal lung tissues through filtering the genomic sequence of the normal lung tissues against that of the paired tumors, the reference human genome, the dbSNP138 common germline variants, and the variations derived from sequencing artifacts. To expand these observations, the whole exome sequences of 478 counterpart normal controls （CNCs） and paired LUSCs of The Cancer Genome Atlas （TCGA） dataset were analyzed. Sixteen genomic variations were called in the three normal lung tissues. These variations were confirmed by Sanger capillary sequencing. A mean of 0.5661 exonic variations/Mb and 7.7887 altered genes per sample were identified in the CNC genome sequences of TCGA. In these CNCs, C：G→T：A transitions, which are the genomic signatures of tobacco carcinogen N-methyl-N-nitro-N-nitrosoguanidine, were the predominant nucleotide changes. Twenty five genes in CNCs had a variation rate that exceeded 2%, including ARSD （18.62%）, MUC4 （8.79%）, and RBMX（7.11%）. CNC variations in CTAGE5 and USP17L7were associated with the poor prognosis of patients with LUSC. Our results uncovered previously unreported genomic variations in CNCs, rather than LUSCs, that may be involved in the develooment of LUSC.展开更多
文摘肿瘤是由多基因变异引起蛋白功能改变并长期积累所致,属于基因病范畴。基因变异能够直接或间接地影响肿瘤的增殖、侵袭和转移等生理病理过程,与肿瘤的发生发展密切相关。基因组中包含丰富的遗传变异类型,其中单核苷酸多态性(single nucleotide polymorphism,SNP)、插入/缺失(insertion/deletion,Indel)和拷贝数变异(copy number variation,CNV)最为多见。本文介绍了三种变异在乳腺癌发生发展中的作用,并展望了其作为潜在的分子标记在乳腺癌临床诊断、治疗及预后评估等方面的应用前景。
基金This work was supported by the National Natural Science Funds of China for Distinguished Young Scholar （No. 81425025）, the National Key Research and Development Program of China （No. 2016YFC0905500）, the National Natural Science Foundation of China （No. 81672765）, the Strategic Priority Research Program of the Chinese Academy of Sciences （No. XDA 12010307）, and grants from the State Key Laboratory of Membrane Biology. The funders had no role in the design, data collection, and analysis of the study or in the preparation of and the decision to publish the manuscript. The results shown here are partly based on the data generated by The Cancer Genome Atlas, which is managed by the NCI and NHGRI. Information about TCGA can be found at http：//cancergenome.nih. gov. The dbGaP accession number is phs000178.v9.p8.
文摘Lung squamous cell carcinoma （LUSC） causes approximately 400 000 deaths each year worldwide. The occurrence of LUSC is attributed to exposure to cigarette smoke, which induces the development of numerous genomic abnormalities. However, few studies have investigated the genomic variations that occur only in normal tissues that have been similarly exposed to tobacco smoke as tumor tissues. In this study, we sequenced the whole genomes of three normal lung tissue samples and their paired adjacent squamous cell carcinomas. We then called genomic variations specific to the normal lung tissues through filtering the genomic sequence of the normal lung tissues against that of the paired tumors, the reference human genome, the dbSNP138 common germline variants, and the variations derived from sequencing artifacts. To expand these observations, the whole exome sequences of 478 counterpart normal controls （CNCs） and paired LUSCs of The Cancer Genome Atlas （TCGA） dataset were analyzed. Sixteen genomic variations were called in the three normal lung tissues. These variations were confirmed by Sanger capillary sequencing. A mean of 0.5661 exonic variations/Mb and 7.7887 altered genes per sample were identified in the CNC genome sequences of TCGA. In these CNCs, C：G→T：A transitions, which are the genomic signatures of tobacco carcinogen N-methyl-N-nitro-N-nitrosoguanidine, were the predominant nucleotide changes. Twenty five genes in CNCs had a variation rate that exceeded 2%, including ARSD （18.62%）, MUC4 （8.79%）, and RBMX（7.11%）. CNC variations in CTAGE5 and USP17L7were associated with the poor prognosis of patients with LUSC. Our results uncovered previously unreported genomic variations in CNCs, rather than LUSCs, that may be involved in the develooment of LUSC.
文摘轮状病毒(RV)细胞培养问题迄今尚未完全解决。为此,我们从筛选RV 敏感细胞和改变 RV 培养条件入手研究,发现恒河猴胚肾传代细胞 Frhk-4对不同血清型的人和动物 RV 标准株敏感,感染后有明显 CPE。将刀豆素 A(Con A)加入营养液中,在细胞生长过程中预处理细胞时,能显著增加 Wa 株的空斑数目和增殖滴度,加速 CPE 的发展,而用 Con A 预处理病毒、加入病毒接种液或加入凝胶覆盖物时,则明显抑制 Wa 株的空斑形成。此外,我们发现,Wa 株经细胞培养多次传代后,有变异株产生,所分离到的3个克隆株的基因图谱与原始 Wa 株有明显差异。对此,国内外均未见报道。
