ESRRA-C11orf20 is a recurrent gene fusion in serous ovarian carcinoma.
ESRRA-C11orf20 is a recurrent gene fusion in serous ovarian carcinoma.
复制标题
DOI：
10.1371/journal.pbio.1001156
复制
发表时间：
2011-09
期刊：
影响因子：
9.8
通讯作者：
Brown PO
中科院分区：
文献类型：
--
作者：
Salzman J;Marinelli RJ;Wang PL;Green AE;Nielsen JS;Nelson BH;Drescher CW;Brown PO
许多卵巢癌有一个染色体重排融合两个相邻的基因，ESRRA和c11 orf 20。类似的重排可能是癌症基因组中常见的重要特征，这些特征在很大程度上逃脱了检测。每年，卵巢癌在美国杀死大约14，000名妇女，在全世界杀死超过140，000名妇女。这些死亡大多数是由浆液性组织学类型的肿瘤引起的，这种肿瘤在扩散之前很少被诊断出来。通过对来自浆液性卵巢癌的mRNA进行深度配对末端测序，然后对相应的基因组区域进行深度测序，我们鉴定了一种复发性融合转录本。融合转录本将编码核激素受体超家族配体非依赖性成员的ESRRA的5′外显子连接到C11 orf 20的3′外显子，C11 orf 20是一个保守但未表征的基因，位于参考基因组中ESRRA的上游。为了估计融合的患病率，我们通过RT-PCR和测序检测了67例浆液性卵巢癌，并证实其中10例存在融合。两个融合阳性肿瘤样本的相应基因组区域的靶向重测序确定了一个肿瘤中C11 orf 20上游ESRRA定位的近克隆染色体重排，以及第二个肿瘤中ESRRA基因座中局部拷贝数变异的证据。我们推测，复发性新的融合转录物可能在相当一部分浆液性卵巢癌的发病机制中发挥作用，并可能为癌症的检测提供分子标记。涉及相邻或邻近基因的基因融合可以容易地逃避检测，但可能在癌症的发展和进展中起重要作用。浆液性卵巢癌是卵巢癌最常见的形式，特别致命，因为它通常只在癌症扩散到其他组织后的晚期阶段才被发现。我们寻找这种癌症的分子标记物，这些标记物可能提供一种更好的方法来检测处于可治愈阶段的肿瘤，并可能为新的治疗提供靶点。融合两个基因以产生增强癌症生长或扩散的重组基因的染色体重排是特别特异的生物标志物，并且已经在许多癌症中发现。通过对浆液性卵巢癌中携带遗传信息的RNA分子进行“深度”测序，我们发现了一种重排，这种重排在至少15%的这些肿瘤中融合了相同的两个相邻基因。这两个融合的基因是ESRRA，它编码基因表达的关键调节因子，和一个基本上没有特征的基因，C11 orf 20，它通常与ESRRA基因相邻。重组两个相邻基因的部分或甚至单个基因的部分的染色体重排可能是癌症基因组的一个常见的重要特征，其逃避了大多数表征癌症基因组的方法的检测。
Many ovarian cancers have a chromosomal rearrangement that fuses two neighboring genes, ESRRA and c11orf20. Similar rearrangements may be common, important features of cancer genomes that have largely escaped detection. Every year, ovarian cancer kills approximately 14,000 women in the United States and more than 140,000 women worldwide. Most of these deaths are caused by tumors of the serous histological type, which is rarely diagnosed before it has disseminated. By deep paired-end sequencing of mRNA from serous ovarian cancers, followed by deep sequencing of the corresponding genomic region, we identified a recurrent fusion transcript. The fusion transcript joins the 5′ exons of ESRRA, encoding a ligand-independent member of the nuclear-hormone receptor superfamily, to the 3′ exons of C11orf20, a conserved but uncharacterized gene located immediately upstream of ESRRA in the reference genome. To estimate the prevalence of the fusion, we tested 67 cases of serous ovarian cancer by RT-PCR and sequencing and confirmed its presence in 10 of these. Targeted resequencing of the corresponding genomic region from two fusion-positive tumor samples identified a nearly clonal chromosomal rearrangement positioning ESRRA upstream of C11orf20 in one tumor, and evidence of local copy number variation in the ESRRA locus in the second tumor. We hypothesize that the recurrent novel fusion transcript may play a role in pathogenesis of a substantial fraction of serous ovarian cancers and could provide a molecular marker for detection of the cancer. Gene fusions involving adjacent or nearby genes can readily escape detection but may play important roles in the development and progression of cancer. Serous ovarian cancer, the most common form of ovarian cancer, is especially lethal because it is usually only detected at a late stage in its progression, after the cancer has spread to other tissues. We searched for molecular markers of this cancer that might provide a better way to detect tumors at a curable stage and that might provide targets for new treatments. Chromosomal rearrangements that fuse two genes to produce a recombinant gene that enhances growth or spread of the cancer are particularly specific biomarkers and have been found in many cancers. By “deep” sequencing of the RNA molecules that carry genetic information in serous ovarian cancers, we discovered a rearrangement that fuses the same two neighboring genes in at least 15% of these tumors. The two fused genes are ESRRA, which encodes a key regulator of gene expression, and an essentially uncharacterized gene, C11orf20, that is normally adjacent to the ESRRA gene. Chromosomal rearrangements that recombine parts of two nearby genes or even parts of a single gene may be a common, important feature of the cancer genome that eludes detection by most approaches to characterizing cancer genomes.
登录
查看更多内容
DOI：
10.1158/1055-9965.epi-10-1224
发表时间：
2011-06
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Permuth-Wey J;Chen YA;Tsai YY;Chen Z;Qu X;Lancaster JM;Stockwell H;Dagne G;Iversen E;Risch H;Barnholtz-Sloan J;Cunningham JM;Vierkant RA;Fridley BL;Sutphen R;McLaughlin J;Narod SA;Goode EL;Schildkraut JM;Fenstermacher D;Phelan CM;Sellers TA
通讯作者：
Sellers TA
影响因子：
12.3
作者：
Pang, Andy W.;MacDonald, Jeffrey R.;Scherer, Stephen W.
通讯作者：
Scherer, Stephen W.
影响因子：
5.7
作者：
Salzman, Julia;Jiang, Hui;Wong, Wing Hung
通讯作者：
Wong, Wing Hung
DOI：
10.1080/01635580802666281
发表时间：
2009
期刊：
Nutrition and cancer
影响因子：
--
作者：
Luo H;Rankin GO;Liu L;Daddysman MK;Jiang BH;Chen YC
通讯作者：
Chen YC
影响因子：
7
作者：
Berger, Michael F.;Levin, Joshua Z.;Garraway, Levi A.
通讯作者：
Garraway, Levi A.