Genomic aberrations in lung adenocarcinoma in never smokers.
Genomic aberrations in lung adenocarcinoma in never smokers.
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DOI：
10.1371/journal.pone.0015145
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发表时间：
2010-12-06
期刊：
影响因子：
3.7
通讯作者：
LG Investigators
中科院分区：
文献类型：
--
作者：
Job B;Bernheim A;Beau-Faller M;Camilleri-Broët S;Girard P;Hofman P;Mazières J;Toujani S;Lacroix L;Laffaire J;Dessen P;Fouret P;LG Investigators
从不吸烟者的肺癌将成为全球第七大最常见的癌症死亡原因。我们对 60 名从不吸烟者的肺腺癌进行了高分辨率阵列比较基因组杂交分析，并确定了 14 个新的增益或缺失的最小共同区域 (MCR)，其中 5 个包含单个基因（MOCS2、NSUN3、KHDRBS2、SNTG1 和 ST18）。一个较大的 MCR 增益包含 NSD1。 1 个焦点放大和 9 个增益包含 FUS。 NSD1 和 FUS 是迄今为止未知与肺癌相关的癌基因。 FISH 显示包含 FUS 的扩增子在 16p11.2 处与下一个端粒扩增子连接。 FUS 在 10 个肿瘤中过度表达，增加了 16p11.2，而 30 个肿瘤没有增加 16p11.2。畸变中存在的其他癌症基因包括 ARNT、BCL9、CDK4、CDKN2B、EGFR、ERBB2、MDM2、MDM4、MET、MYC 和 KRAS。通过调整错误发现率的无监督分层聚类揭示了因畸变水平和模式而异的簇，并显示出特定的肿瘤特征。其中一簇与 MYC 的增加密切相关。另一个簇的特征是含有肿瘤抑制基因（其中RB1和WRN）的大量损失。该簇中的肿瘤经常具有中央疤痕样纤维化。第三个簇与 7p 和 7q 的增益相关，包含 ETV1 和 BRAF，并且显示出最高的 EGFR 突变率。 SNP 阵列分析验证了拷贝数畸变，并揭示了 RB1 和 WRN 因反复出现的拷贝中性杂合性丢失而改变。目前的研究发现了含有癌症基因的新畸变。癌基因 FUS 是 16p 区域的候选基因，在从不吸烟的人中经常出现。由 MYC 增加、RB1 和 WRN 缺失或 7p 和 7q 增加定义的多种遗传途径与从不吸烟者的肺腺癌有关。
Lung cancer in never smokers would rank as the seventh most common cause of cancer death worldwide. We performed high-resolution array comparative genomic hybridization analysis of lung adenocarcinoma in sixty never smokers and identified fourteen new minimal common regions (MCR) of gain or loss, of which five contained a single gene (MOCS2, NSUN3, KHDRBS2, SNTG1 and ST18). One larger MCR of gain contained NSD1. One focal amplification and nine gains contained FUS. NSD1 and FUS are oncogenes hitherto not known to be associated with lung cancer. FISH showed that the amplicon containing FUS was joined to the next telomeric amplicon at 16p11.2. FUS was over-expressed in 10 tumors with gain of 16p11.2 compared to 30 tumors without that gain. Other cancer genes present in aberrations included ARNT, BCL9, CDK4, CDKN2B, EGFR, ERBB2, MDM2, MDM4, MET, MYC and KRAS. Unsupervised hierarchical clustering with adjustment for false-discovery rate revealed clusters differing by the level and pattern of aberrations and displaying particular tumor characteristics. One cluster was strongly associated with gain of MYC. Another cluster was characterized by extensive losses containing tumor suppressor genes of which RB1 and WRN. Tumors in that cluster frequently harbored a central scar-like fibrosis. A third cluster was associated with gains on 7p and 7q, containing ETV1 and BRAF, and displayed the highest rate of EGFR mutations. SNP array analysis validated copy-number aberrations and revealed that RB1 and WRN were altered by recurrent copy-neutral loss of heterozygosity. The present study has uncovered new aberrations containing cancer genes. The oncogene FUS is a candidate gene in the 16p region that is frequently gained in never smokers. Multiple genetic pathways defined by gains of MYC, deletions of RB1 and WRN or gains on 7p and 7q are involved in lung adenocarcinoma in never smokers.
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DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
8
作者：
Kanoe, H;Nakayama, T;Toguchida, J
通讯作者：
Toguchida, J
影响因子：
158.5
作者：
Mok, Tony S.;Wu, Yi-Long;Fukuoka, Masahiro
通讯作者：
Fukuoka, Masahiro
影响因子：
8
作者：
Garnis, C;Davies, JJ;Lam, WL
通讯作者：
Lam, WL
影响因子：
6.4
作者：
Garnis, C;Lockwood, WW;Lam, WL
通讯作者：
Lam, WL