Histotype-specific copy-number alterations in ovarian cancer.
Histotype-specific copy-number alterations in ovarian cancer.
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DOI：
10.1186/1755-8794-5-47
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发表时间：
2012-10-18
影响因子：
2.7
通讯作者：
Goh L
中科院分区：
文献类型：
--
作者：
Huang RY;Chen GB;Matsumura N;Lai HC;Mori S;Li J;Wong MK;Konishi I;Thiery JP;Goh L
上皮性卵巢癌以多种基因组改变为特征；大多数是乘客改变，不会导致肿瘤生长。像许多癌症一样，它是一种异质性疾病，大致可分为4种主要组织类型：透明细胞、子宫内膜样变、粘液性和浆液性。到目前为止，组织类型特异性拷贝数的改变还很难阐明。困难在于在每个组织类型中有足够的样本大小用于统计分析。为了剖析卵巢癌的异质性并确定组织类型特异性的改变，我们在上皮性卵巢癌的多个数据集上使用了电子假说驱动的方法。与之前关于全球拷贝数变化的研究一致，这项研究显示了类似的变化。然而，当景观被分解成组织类型时，观察到了明显的变化。我们在这里报道了卵巢癌组织类型特异性拷贝数的显著改变，并表明在组织类型中存在基因组多样性。发现76个癌基因发生显著改变，其中几个是潜在的拷贝数驱动因素，包括粘液性组织中的ERBB2和子宫内膜样组织类型中的TPM3。ERBB2在粘液性肿瘤中扩增(28.6%)，在浆液性肿瘤中缺失(15.1%)。ERBB2表达的验证与微阵列数据有显著相关性(p=0.007)。KRAS突变和拷贝数改变之间似乎也存在相互作用的关系。在粘液性肿瘤中，KRAS突变很常见，该基因没有明显改变。然而，KRAS在浆液性肿瘤中显著扩增，而在高级别肿瘤中突变很少。研究表明，拷贝数图谱是特定于组织类型的，识别这些改变可以为针对组织类型的靶向药物治疗铺平道路。
Epithelial ovarian cancer is characterized by multiple genomic alterations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and can be broadly categorized into 4 main histotypes of clear cell, endometrioid, mucinous, and serous. To date, histotype-specific copy number alterations have been difficult to elucidate. The difficulty lies in having sufficient sample size in each histotype for statistical analyses. To dissect the heterogeneity of ovarian cancer and identify histotype-specific alterations, we used an in silico hypothesis-driven approach on multiple datasets of epithelial ovarian cancer. In concordance with previous studies on global copy number alterations landscape, the study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here significant histotype-specific copy number alterations in ovarian cancer and showed that there is genomic diversity amongst the histotypes. 76 cancer genes were found to be significantly altered with several as potential copy number drivers, including ERBB2 in mucinous, and TPM3 in endometrioid histotypes. ERBB2 was found to have preferential alterations, where it was amplified in mucinous (28.6%) but deleted in serous tumors (15.1%). Validation of ERBB2 expression showed significant correlation with microarray data (p=0.007). There also appeared to be reciprocal relationship between KRAS mutation and copy number alterations. In mucinous tumors where KRAS mutation is common, the gene was not significantly altered. However, KRAS was significantly amplified in serous tumors where mutations are rare in high grade tumors. The study demonstrates that the copy number landscape is specific to the histotypes and identification of these alterations can pave the way for targeted drug therapy specific to the histotypes.
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影响因子：
24.5
作者：
Deng N;Goh LK;Wang H;Das K;Tao J;Tan IB;Zhang S;Lee M;Wu J;Lim KH;Lei Z;Goh G;Lim QY;Tan AL;Sin Poh DY;Riahi S;Bell S;Shi MM;Linnartz R;Zhu F;Yeoh KG;Toh HC;Yong WP;Cheong HC;Rha SY;Boussioutas A;Grabsch H;Rozen S;Tan P
通讯作者：
Tan P
影响因子：
7.3
作者：
Ahmed, Ashour Ahmed;Etemadmoghadam, Dariush;Temple, Jillian;Lynch, Andy G.;Riad, Mohamed;Sharma, Raghwa;Stewart, Colin;Fereday, Sian;Caldas, Carlos;DeFazio, Anna;Bowtell, David;Brenton, James D.
通讯作者：
Brenton, James D.
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：
--
DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
2
作者：
Chuaqui, R F;Cole, K A;Merino, M J
通讯作者：
Merino, M J