Driver mutations among never smoking female lung cancer tissues in China identify unique EGFR and KRAS mutation pattern associated with household coal burning.
Driver mutations among never smoking female lung cancer tissues in China identify unique EGFR and KRAS mutation pattern associated with household coal burning.
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DOI：
10.1016/j.rmed.2013.08.018
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发表时间：
2013-11
影响因子：
4.3
通讯作者：
Lan, Qing
中科院分区：
文献类型：
--
作者：
Hosgood, H. Dean, III;Pao, William;Rothman, Nathaniel;Hu, Wei;Pan, Yumei Helen;Kuchinsky, Kyle;Jones, Kirk D.;Xu, Jun;Vermeulen, Roel;Simko, Jeff;Lan, Qing
从不吸烟者的肺癌，部分归因于家庭固体燃料的使用（即煤），在病因和临床上与归因于吸烟的肺癌不同。为了探索从不吸烟者的肺癌组织中的驱动突变谱，特别是在高肺癌率归因于家庭煤炭使用的室内空气污染的人群中，使用多重测定来检测>40个点突变、插入和缺失。来自中国宣威的确诊的从不吸烟女性的肺肿瘤中的EGFR、KRAS、BRAF、HER2、NRAS、PIK3CA、MEK 1、AKT1和PTEN的表达[32例腺癌（ADC），7例鳞状细胞癌（SCC），1例腺鳞癌（ADSC）]。在35%的肿瘤中检测到EGFR突变。其中46%涉及EGFR外显子18 G719X，而14%为外显子21 L858R突变。在15%的肿瘤中观察到KRAS突变，所有突变均为G12C_34G>T。EGFR和KRAS突变相互排斥，在其他检测基因中未观察到突变。大多数点突变是颠换，也在家中使用煤炭的患者的肿瘤中发现。我们的EGFR外显子18和KRAS的高突变频率和EGFR外显子21的低突变频率与亚洲其他吸烟和从不吸烟人群的突变频率显著不同。鉴于我们的研究对象生活在一个煤炭通常在室内燃烧的地区，我们的研究结果为暴露于煤炭室内空气污染的从不吸烟女性肺癌发病机制提供了新的见解。
Lung cancer in never smokers, which has been partially attributed to household solid fuel use (i.e coal), is etiologically and clinically different from lung cancer attributed to tobacco smoking. To explore the spectrum of driver mutations among lung cancer tissues from never smokers, specifically in a population where high lung cancer rates have been attributed to indoor air pollution from domestic coal use, multiplexed assays were used to detect >40 point mutations, insertions, and deletions (EGFR, KRAS, BRAF, HER2, NRAS, PIK3CA, MEK1, AKT1, and PTEN) among the lung tumors of confirmed never smoking females from Xuanwei, China [32 adenocarcinomas (ADCs), 7 squamous cell carcinomas (SCCs), 1 adenosquamous carcinoma (ADSC)]. EGFR mutations were detected in 35% of tumors. 46% of these involved EGFR exon 18 G719X, while 14% were exon 21 L858R mutations. KRAS mutations, all of which were G12C_34G>T, were observed in 15% of tumors. EGFR and KRAS mutations were mutually exclusive, and no mutations were observed in the other tested genes. Most point mutations were transversions and were also found in tumors from patients who used coal in their homes. Our high mutation frequencies in EGFR exon 18 and KRAS and low mutation frequency in EGFR exon 21 are strikingly divergent from those in other smoking and never smoking populations from Asia. Given that our subjects live in a region where coal is typically burned indoors, our findings provide new insights into the pathogenesis of lung cancer among never smoking females exposed to indoor air pollution from coal.
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东亚从不吸烟者肺腺癌的致癌驱动突变谱
影响因子：
3.7
作者：
Li C;Fang R;Sun Y;Han X;Li F;Gao B;Iafrate AJ;Liu XY;Pao W;Chen H;Ji H
通讯作者：
Ji H
DOI：
10.1080/00039896.1988.9935850
发表时间：
1988-03-01
期刊：
ARCHIVES OF ENVIRONMENTAL HEALTH
影响因子：
--
作者：
CHAPMAN, RS;MUMFORD, JL;YANG, RD
通讯作者：
YANG, RD
影响因子：
8.8
作者：
Hosgood, H. D., III;Chapman, R.;Shen, M.;Blair, A.;Chen, E.;Zheng, T.;Lee, K-M;He, X.;Lan, Q.
通讯作者：
Lan, Q.
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
4.7
作者：
Mumford, JL;Li, XM;Chuang, JC
通讯作者：
Chuang, JC