乳がんは拡大中にサブクローン多様性の貯蔵庫を維持する
Darlan C Minussi1,2, Michael D Nicholson3,4,5, Hanghui Ye1,2
1Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nature
|March 25, 2021
まとめ
トリプルネガティブな乳がんは 重要なサブクローン多様性と進行中のゲノム進化を示しています 単細胞配列解析は,原発腫瘍内の複合的なコピー数変化と多様化を明らかにする.
科学分野:
- ゲノミクス
- 癌 生物学
- 進化生物学
背景:
- 乳がんの原発的な成長過程における複製数の変化に関する理解は限られている.
- 腫瘍の異質性を高解像度で分析する必要がある.
研究 の 目的:
- 単細胞解像度でのトリプルネガティブ乳がんの複製数の進化を調査する.
- 主要腫瘍のサブクローン構造と進化動態を特徴付ける.
主な方法:
- 単細胞単分子DNAの配列決定法を開発しました
- ヒトのトリプルネガティブ乳がんと細胞系から 16,178 個の単細胞の複製数解析を行った.
主要な成果:
- 腫瘍ごとに3〜5の主要なスーパークローンに編成された7〜22のサブクローンを特定した.
- TP53後のゲノム倍増と一時的なゲノム不安定が観察されました.
- 腫瘍細胞ゲノムの進行中の複製数進化と多様化を実証した.
結論:
- トリプルネガティブな乳がんは,原発腫瘍の拡大中に実質的なサブクローン多様性を維持する.
- 腫瘍細胞は染色体異常を継続的に進化させ,同位体性にとどまらない.
- 単細胞配列解析は 乳がんの進化について 重要な洞察を与えてくれます
関連する概念動画
Tumor Progression
6.8K
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...
6.8K
Cancer Stem Cells and Tumor Maintenance
5.2K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.2K
Cancer
51.6K
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.
51.6K
Cancers Originate from Somatic Mutations in a Single Cell
13.4K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
13.4K
Adaptive Mechanisms in Cancer Cells
6.1K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.1K
Metastasis
6.0K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
6.0K


