Genomic evidence of lung carcinogenesis associated with coal smoke in Xuanwei area, China.
Genomic evidence of lung carcinogenesis associated with coal smoke in Xuanwei area, China.
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中国宣威地区煤烟相关肺癌的基因组证据
DOI：
10.1093/nsr/nwab152
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发表时间：
2021-12
影响因子：
20.6
通讯作者：
Ye L
中科院分区：
文献类型：
--
作者：
Zhang H;Liu C;Li L;Feng X;Wang Q;Li J;Xu S;Wang S;Yang Q;Shen Z;Su J;Su X;Sun R;Zhou X;Wang J;Zhou Y;Jiao B;Ding W;Cao X;Wang Y;Huang Y;Ye L
宣威地区位于中国西南部，是全国女性肺癌发病率最高的地区（补充表1）。流行病学研究表明，宣威地区的肺癌发病率与家庭使用不同类型的当地煤炭做饭和取暖有关。宣威女性腺癌（XWFA）是宣威地区肺癌最显著的特征，其基因组图谱尚未得到系统的阐明。本研究为进一步探索XWFA分子机制和开发靶向治疗提供了基因组数据的基础资源。本研究招募的患者为来自宣威地区未经治疗的原发性肺腺癌（LUAD）女性非吸烟者117例，在云南省肿瘤医院接受手术治疗（补充表2）。取样本进行全外显子组测序（WES）（112对肿瘤-正常），用mRNA-Seq技术对33例正常和115例肿瘤样本进行测序。采用来自The Cancer Genome Atlas （TCGA）项目的168名TCGA- luad女性吸烟者（TLSF）和102名TCGA- luad女性非吸烟者（TLNF）的数据集，对与香烟相关的肺癌和与煤烟相关的肺癌进行基因组比较（补充表3）。在XWFA、TLSF和TLNF组中，不同病理分期的样本分布无显著差异（图1a）。在XWFA队列中，鉴定出35729个体细胞突变，包括34287个单核苷酸变异（snv）和1442个插入或缺失（In - dels）（补充方法）。与TCGA肺癌样本相比，XWFA样本的突变负担（中位数= 2.11）高于肺鳞状细胞癌（LUSC）（中位数= 1.63）和LUAD（中位数= 1.41）（图2）。1 b)。这表明XWFA和西方队列之间的突变基因组景观存在实质性差异。此外，采用MutSig2CV（软件详见补充方法）和oncodriveCLUST算法联合鉴定XWFA队列中的显著突变基因（smg）。如图1c所示，在XWFA队列中观察到的最突出的癌症相关变异是EGFR突变（在52.68%的肿瘤中发现），其次是TP53突变（41.07%），RBM10
Xuanwei area, in southwestern China, harbors the highest female lung cancer rate in the country (Supplementary Table 1)[1]. Epidemiological studies have shown that lung cancer incidence in Xuanwei area is associated with the use of different types of local coal for household cooking and heating [2]. The genomic landscape of Xuanwei female adenocarcinoma (XWFA), the most distinctive feature of lung cancer in Xuanwei, has yet to be elucidated systematically. Here, we provide the fundamental resource of genomic datasets for further exploration of XWFA molecular mechanisms and development of targetable therapy. The patients recruited for this study were 117 non-smoker females with untreated primary lung adenocarcinoma (LUAD) from the Xuanwei area, who were receiving surgical treatment at Yunnan Cancer Hospital (Supplementary Table 2). Samples were taken for whole-exome sequencing (WES)(112 pairs of tumor-normal), and 33 normal and 115 tumor samples were sequenced with mRNA-Seq technology. Datasets of 168 TCGA-LUAD female smokers (TLSF) and 102 TCGA-LUAD female non-smokers (TLNF) were adopted from The Cancer Genome Atlas (TCGA) program for genomic comparison between lung cancer associated with cigarettes and that associated with smoky coal [3](Supplementary Table 3). There were no significant differences in the distribution of samples from different pathologic stages among the XWFA, TLSF and TLNF cohorts (Fig. 1 a). In the XWFA cohort, 35729 somatic mutations comprising 34287 single-nucleotide variants(SNVs) and 1442 insertions or deletions (IN-DELs) were identified (Supplementary Methods). Compared with the TCGA lung cancer samples, XWFA samples possessed higher mutation burdens (median= 2.11) than lung squamous cell carcinomas (LUSC)(median= 1.63) and LUAD (median= 1.41)(Fig. 1 b). This suggests substantial differences in the mutational genomic landscape between the XWFA and Western cohorts. Furthermore, MutSig2CV (for details of software, refer to the Supplementary Methods) and oncodriveCLUST algorithms were adopted jointly to identify significantly mutated genes (SMGs) in the XWFA cohort. As demonstrated in Fig. 1 c, the most prominent cancerrelated variations observed in the XWFA cohort were EGFR mutations (found in 52.68% of tumors), followed by mutations in TP53 (41.07%), RBM10
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影响因子：
22.7
作者：
Ghorani, Ehsan;Reading, James L.;Quezada, Sergio A.
通讯作者：
Quezada, Sergio A.
影响因子：
56.9
作者：
HOLLSTEIN, M;SIDRANSKY, D;HARRIS, CC
通讯作者：
HARRIS, CC
DOI：
10.1093/jnci/94.11.826
发表时间：
2002-06-05
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Lan, Q;Chapman, RS;He, XZ
通讯作者：
He, XZ
影响因子：
7.3
作者：
Ning Z;Liu K;Xiong H
通讯作者：
Xiong H
影响因子：
4.3
作者：
Upadhyay, Shishir;Vaish, Saurabh;Dhiman, Monisha
通讯作者：
Dhiman, Monisha