Genomic analyses reveal FAM84B and the NOTCH pathway are associated with the progression of esophageal squamous cell carcinoma.
Genomic analyses reveal FAM84B and the NOTCH pathway are associated with the progression of esophageal squamous cell carcinoma.
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基因组分析表明 FAM84B 和 NOTCH 通路与食管鳞状细胞癌的进展相关。
DOI：
10.1186/s13742-015-0107-0
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发表时间：
2016
期刊：
影响因子：
9.2
通讯作者：
Cui Y
中科院分区：
文献类型：
--
作者：
Cheng C;Cui H;Zhang L;Jia Z;Song B;Wang F;Li Y;Liu J;Kong P;Shi R;Bi Y;Yang B;Wang J;Zhao Z;Zhang Y;Hu X;Yang J;He C;Zhao Z;Wang J;Xi Y;Xu E;Li G;Guo S;Chen Y;Yang X;Chen X;Liang J;Guo J;Cheng X;Wang C;Zhan Q;Cui Y
食管鳞状细胞癌（ESCC）是世界上第六大致死性癌症，在中国是第四大致死性癌症。肿瘤的基因组特征，特别是不同阶段的肿瘤，可能揭示其他致癌机制。虽然与ESCC发展相关的拷贝数改变和体细胞点突变已通过基于阵列的技术和全基因组研究确定，但尚未探索来自疾病不同阶段的ESCC的基因组特征。在这里，我们对51例I期和53例III期ESCC患者进行了全基因组测序或全外显子组测序，以表征ESCC不同临床阶段发生的基因组改变，并在36例不典型增生样本中进一步验证了这些变化。发现8 q处的复发性体细胞扩增在I期肿瘤中富集，并且在III期肿瘤中特别鉴定出4p-q和5 q的缺失。特别是，FAM 84 B基因在临床前和ESCC肿瘤中扩增和过表达。ESCC细胞系中FAM 84 B的敲低显著降低体外细胞生长、迁移和侵袭。尽管癌症相关基因TP 53、PIK 3CA、CDKN 2A及其通路在I期和III期肿瘤之间没有显着差异，但我们确定并验证了NOTCH 1和NOTCH通路中突变的普遍性，表明它们参与了ESCC的临床前和早期阶段。我们的研究结果表明，FAM 84 B和NOTCH通路参与了ESCC的进展，并可能成为ESCC易感性的潜在诊断靶点。本文的在线版本（doi：10.1186/s13742-015-0107-0）包含补充材料，可供授权用户使用。
Esophageal squamous cell carcinoma (ESCC) is the sixth most lethal cancer worldwide and the fourth most lethal cancer in China. Genomic characterization of tumors, particularly those of different stages, is likely to reveal additional oncogenic mechanisms. Although copy number alterations and somatic point mutations associated with the development of ESCC have been identified by array-based technologies and genome-wide studies, the genomic characterization of ESCCs from different stages of the disease has not been explored. Here, we have performed either whole-genome sequencing or whole-exome sequencing on 51 stage I and 53 stage III ESCC patients to characterize the genomic alterations that occur during the various clinical stages of ESCC, and further validated these changes in 36 atypical hyperplasia samples. Recurrent somatic amplifications at 8q were found to be enriched in stage I tumors and the deletions of 4p-q and 5q were particularly identified in stage III tumors. In particular, the FAM84B gene was amplified and overexpressed in preclinical and ESCC tumors. Knockdown of FAM84B in ESCC cell lines significantly reduced in vitro cell growth, migration and invasion. Although the cancer-associated genes TP53, PIK3CA, CDKN2A and their pathways showed no significant difference between stage I and stage III tumors, we identified and validated a prevalence of mutations in NOTCH1 and in the NOTCH pathway that indicate that they are involved in the preclinical and early stages of ESCC. Our results suggest that FAM84B and the NOTCH pathway are involved in the progression of ESCC and may be potential diagnostic targets for ESCC susceptibility. The online version of this article (doi:10.1186/s13742-015-0107-0) contains supplementary material, which is available to authorized users.