微环境基因组变化和临床病理行为在头部和部状细胞癌
Frank Weber1, Yaomin Xu, Li Zhang
1Genomic Medicine Institute and Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
JAMA
|January 11, 2007
概括
头支状细胞癌 (SCC) 的基因组变化与疾病的攻击性有关,特别是在吸烟者中. 这些特异性基因变化可以作为预后和治疗点的生物标志物.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 癌症生物学 癌症生物学
背景情况:
- 头部和部状细胞癌 (SCC) 的产生涉及表皮和介质细胞组成部分的基因组变化.
- 瘤侧膜,虽然看似非恶性,但可以获得导致癌症发病和进展的遗传变化.
研究的目的:
- 为了识别分区特定的基因组变化,特别是异合性或等位基因失衡 (LOH/AI) 的损失.
- 为了确定肌体特异性基因组变化是否与头部和部SCC的攻击性相关.
主要方法:
- 全基因组LOH/AI分析对122名头部和部SCC患者的瘤表皮和周围层进行了分析,使用366个微卫星标记物.
- 激光捕获微切割和DNA提取被用于精确的隔离和细分区特异性DNA的基因定型.
主要成果:
- 在吸烟者头部和部SCC患者的瘤关联肌瘤中观察到高程度的基因组变化.
- 三个特定于侧膜位点 (D4S2417,D3S360和D19555) 与瘤大小 (pT) 和结节转移 (pN) 有显著关联.
- 两个表皮特异性的LOH/AI热点也与结节状况和临床阶段相关.
结论:
- 肌瘤特异性遗传变异在吸烟相关的头SCC的发展中起作用.
- 这些发现突出了潜在的预后/诊断生物标志物和头癌干预的新分子标.
相关概念视频
Mutations
Overview
Cancer
Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
The Tumor Microenvironment
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
Mutations
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
The Tumor Microenvironment
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...


