The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA.
Nat Genet. 2012 Oct;44(10):1111-6. doi: 10.1038/ng.2405. Epub 2012 Sep 2.
Small-cell lung cancer (SCLC) is an exceptionally aggressive disease with poor prognosis. Here, we obtained exome, transcriptome and copy-number alteration data from approximately 53 samples consisting of 36 primary human SCLC and normal tissue pairs and 17 matched SCLC and lymphoblastoid cell lines. We also obtained data for 4 primary tumors and 23 SCLC cell lines. We identified 22 significantly mutated genes in SCLC, including genes encoding kinases, G protein-coupled receptors and chromatin-modifying proteins. We found that several members of the SOX family of genes were mutated in SCLC. We also found SOX2 amplification in ∼27% of the samples. Suppression of SOX2 using shRNAs blocked proliferation of SOX2-amplified SCLC lines. RNA sequencing identified multiple fusion transcripts and a recurrent RLF-MYCL1 fusion. Silencing of MYCL1 in SCLC cell lines that had the RLF-MYCL1 fusion decreased cell proliferation. These data provide an in-depth view of the spectrum of genomic alterations in SCLC and identify several potential targets for therapeutic intervention.
小细胞肺癌（SCLC）是一种侵袭性极强、预后较差的疾病。在这里，我们从大约 53 个样本中获得了外显子、转录组和拷贝数改变数据，这些样本包括 36 对原发性人类 SCLC 和正常组织，以及 17 对匹配的 SCLC 和淋巴母细胞系。我们还获得了 4 个原发性肿瘤和 23 个 SCLC 细胞系的数据。我们在 SCLC 中鉴定出 22 个明显突变的基因，包括编码激酶、G 蛋白偶联受体和染色质修饰蛋白的基因。我们发现 SCLC 中几个 SOX 家族基因发生了突变。我们还发现约 27%的样本中存在 SOX2 扩增。使用 shRNA 抑制 SOX2 可阻断 SOX2 扩增的 SCLC 系的增殖。RNA 测序鉴定出多个融合转录本和一个复发性 RLF-MYCL1 融合。沉默 SCLC 细胞系中存在 RLF-MYCL1 融合的 MYCL1 可降低细胞增殖。这些数据提供了 SCLC 中基因组改变谱的深入视图，并确定了几个潜在的治疗干预靶点。
