鉴定食道状细胞癌的基因组变异
Yongmei Song1, Lin Li2, Yunwei Ou3
11] State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China [2].
Nature
|March 28, 2014
概括
这项研究全面分析了食道状细胞癌 (ESCC) 的基因组学,确定了新的突变基因,如FAM135B和瘤性微RNA MIR548K. 研究结果揭示了这种侵袭性癌症的新治疗点和途径.
科学领域:
- 基因组学和瘤学
- 癌症发病的研究 癌症发病的研究
背景情况:
- 食道癌是一种高度侵袭性的恶性瘤,食道状细胞癌 (ESCC) 是中国的主要形式.
- 早期诊断和治疗选择有限,导致ESCC患者的五年生存率为10%.
- 驱动ESCC病原体的完整基因组景观在很大程度上仍未定义.
研究的目的:
- 对大量ESCC病例进行全面的基因组分析.
- 识别涉及ESCC发展的新型遗传变异,突变基因和瘤性途径.
- 发现潜在的新生物标志物和治疗目标,以改进ESCC治疗策略.
主要方法:
- 在ESCC样本上进行了全基因组测序 (WGS) 和全外因组测序 (WES).
- 使用数组比较基因组杂交 (aCGH) 来分析副本数量变异.
- 进行了功能性测试,以验证已识别的基因和microRNAs的致癌潜力.
主要成果:
- 确定了8个显著突变的基因,包括两个新的ESCC相关基因:ADAM29和FAM135B.
- 发现了MIR548K,一个在放大区域中的微RNA,作为一种促进ESCC恶性瘤的新瘤基因.
- 发现了基因调节基因的频繁变化,并确定了关键受影响的途径:Wnt,细胞周期和Notch.
结论:
- 这项研究阐明了ESCC中关键的基因组事件和途径,突出了FAM135B和MIR548K作为新瘤基因.
- 观察到与头部和部状细胞癌的基因组相似性,以及与酒精消费的联系.
- 这些发现为开发改善食道状细胞癌的诊断和治疗策略提供了基础.
相关概念视频
02:54Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
01:20Histology of the Gastrointestinal (GI) Tract
The GI tract, from beginning to end, is made up of four continuous tissue layers that adjust their structure according to their specific roles. These layers, from innermost to outermost, are known as the mucosa, submucosa, muscularis, and serosa, which are continuous with the mesentery.
The mucosa is sometimes called a mucous membrane due to its mucus-secreting features. This membrane is composed of epithelium, which directly interacts with ingested substances, and the lamina propria, a layer...
The mucosa is sometimes called a mucous membrane due to its mucus-secreting features. This membrane is composed of epithelium, which directly interacts with ingested substances, and the lamina propria, a layer...
01:16Gastric Motility
Gastric motility is the coordinated contraction and relaxation of stomach muscles that convert ingested food into chyme, a semi-liquid substance ready for further digestion in the intestines. The process begins with the vagus nerve inducing the relaxation of the smooth muscles in the fundus and body of the stomach, allowing these regions to expand and accommodate up to approximately 1.5 liters of food and liquid.
Peristaltic Waves and Chyme Formation
Upon food entry, the stomach initiates...
Peristaltic Waves and Chyme Formation
Upon food entry, the stomach initiates...
01:27Histology of the Small Intestine
The small intestine exhibits a unique histological structure that significantly enhances its function in digestion and nutrient absorption. These structures include circular folds, villi, and various specialized cells that collectively facilitate the digestion of food.
The intestinal lining features transverse folds called circular folds, each housing fingerlike projections known as intestinal villi. These villi are covered by a layer of simple columnar epithelium, also referred to as...
The intestinal lining features transverse folds called circular folds, each housing fingerlike projections known as intestinal villi. These villi are covered by a layer of simple columnar epithelium, also referred to as...
01:30Other Disorders of Digestive System
The gastrointestinal tract is susceptible to various disorders. If the lower esophageal sphincter is damaged, stomach acid can flow back into the esophagus, causing irritation and inflammation of the lining. This condition is called gastroesophageal reflux disease (known as heartburn) and may cause chest pain and difficulty swallowing. In the stomach, prolonged use of nonsteroidal anti-inflammatory drugs like aspirin, chronic alcohol consumption, bacterial infections such as Helicobacter...
01:29Gastroesophageal Reflux Disease I: Meaning and Pathophysiology
Gastroesophageal Reflux Disease (GERD) involves the recurrent backflow of the stomach or duodenal contents into the esophagus, leading to troublesome symptoms and potential esophageal mucosal damage. Although GERD is often referred to as a disease, it is more accurately described as a syndrome, as it encompasses a range of symptoms and complications rather than a singular pathological entity, impacting a large number of individuals as the most prevalent upper gastrointestinal problem. Roughly...