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从25,000名患者的潜在临床测序中对转移模式的基因组特征

Bastien Nguyen ¹, Christopher Fong ¹, Anisha Luthra ¹

¹Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
²Molecular Pharmacology Program, Sloan Kettering Institute, New York, NY, USA; Urology and Renal Transplantation Service, Virginia Mason Medical Center, Seattle, WA, USA.
³Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College at Cornell University, New York, NY, USA.
⁴Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁵Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Neurology and Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁶Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁷Molecular Pharmacology Program, Sloan Kettering Institute, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁸Weill Medical College at Cornell University, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁹Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁰Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹¹Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹²Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹³Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁴Cancer Biology and Genetics Program, Sloan Kettering Institute, New York, NY, USA.
¹⁵Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁶Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College at Cornell University, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁷Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁸Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

⁰Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

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2022年二月5日

在PubMed上查看摘要

概括

基因组的改变导致癌症转移, 这项研究分析了25,000名转移性癌症患者,揭示了基因组变化,染色体不稳定性和50种瘤转移性传播之间的联系.

科学领域

癌症学
基因组学
癌症转移

背景情况

转移性进展是癌症相关死亡的主要原因.
转移的基因组基础尚未完全理解.
对转移驱动因素的全面了解对于开发有效疗法至关重要.

研究的目的

研究导致不同癌症类型转移的基因组机制.
确定基因组变化与转移传播模式之间的关联.
探索染色体不稳定性在转移负担中的作用.

主要方法

组建了MSK-MET全癌症队列,包括超过25,000名转移性疾病患者.
分析了来自队列的综合基因组和临床数据.
与50种瘤类型的转移负担和模式相关的基因组变化.

主要成果

确定了特定基因组变化和转移性传播模式之间的显著关联.
在某些癌症 (如前列腺癌,肺癌,乳腺癌) 中发现染色体不稳定与转移负担有很强的相关性,但在其他癌症 (如结肠直肠癌,卵巢癌) 中却没有.
发现与转移负担和特定器官热带相关的体质变化,表明不同的转移途径.

结论

基因组变化在驱动癌症转移中起着复杂的作用.
染色体不稳定对转移负担的贡献因不同瘤类型而异.
对于进一步研究癌症传播的生物学基础和确定治疗点,MSK-MET队列提供了宝贵的资源.

关键词:

DNA 测序癌症临床测序基因组学发生转移分子造型突变下一代测序有机化胰腺癌