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Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting
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マイクロ環境のゲノム変異と頭頸部状細胞癌における臨床病理学的行動
Frank Weber1, Yaomin Xu, Li Zhang
1Genomic Medicine Institute and Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
JAMA
|January 11, 2007
まとめ
頭頸部状細胞癌 (SCC) のストロマのゲノム変異は,特に喫煙者において,疾患の攻撃性に関連しています. これらのストロマ特有の遺伝的変化は,予後と治療目標のためのバイオマーカーとして機能する可能性があります.
科学分野:
- 腫瘍学 腫瘍学
- 遺伝学 遺伝学とは
- 癌生物学 癌生物学について
背景:
- 頭頸部状細胞癌 (SCC) の発生には,上皮細胞と中皮細胞の両方の成分におけるゲノム変化が含まれます.
- 腫瘍のストロマは,悪性ではないように見えますが,癌の発生と進行に貢献する遺伝的変化を取得することができます.
研究 の 目的:
- コンパートメント特有のゲノム変異,特にヘテロジゴシティの喪失またはアレル不均衡 (LOH/AI) を特定するために.
- ストロマ特有のゲノム変異が頭頸SCCの攻撃性と相関するかどうかを判断する.
主な方法:
- 全ゲノムLOH/AI分析は,366個のマイクロサテライトマーカーを使用して,頭頸部SCCを有する122人の患者の腫瘍表皮と周囲のストロマを分析した.
- レーザーキャプチャマイクロ解剖とDNA抽出は,コンパートメント特異のDNAの正確な分離とゲノタイプ化のために使用されました.
主要な成果:
- 高度なゲノム変異は,喫煙者であった頭頸部SCC患者の腫瘍関連ストロマで観察されました.
- 3つのストロマ特異的位置 (D4S2417,D3S360およびD19555) は,腫瘍サイズ (pT) と結節転移 (pN) と有意に関連していました.
- 2つの上皮特異的なLOH/AIホットスポットも,結節状態と臨床段階と相関していました.
結論:
- ストロマ特有の遺伝子変異は,喫煙に関連する頭頸部SCCの発生に役割を果たします.
- これらの発見は,潜在的な予後/診断バイオマーカーと,頭頸部がん介入のための新しい分子標的を強調しています.
関連する概念動画
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...

