2025-06-02 メモリアル・スローン・ケタリングがんセンター(MSKCC)
<関連情報>
- https://www.mskcc.org/news/study-provides-new-insights-into-genetic-complexity-of-cancer-metastasis
- https://www.nature.com/articles/s41588-025-02204-3
転移性播種における腫瘍の突然変異とコピー数の進化を縦断的かつ多サイトサンプリングで明らかにする Longitudinal and multisite sampling reveals mutational and copy number evolution in tumors during metastatic dissemination
Karena Zhao,Joris Vos,Stanley Lam,Lillian A. Boe,Daniel Muldoon,Catherine Y. Han,Cristina Valero,Mark Lee,Conall Fitzgerald,Andrew S. Lee,Manu Prasad,Swati Jain,Xinzhu Deng,Timothy A. Chan,Michael F. Berger,Chaitanya Bandlamudi,Xi Kathy Zhou & Luc G. T. Morris
Nature Genetics Published:02 June 2025
DOI:https://doi.org/10.1038/s41588-025-02204-3
Abstract
To understand genetic evolution in cancer during metastasis, we analyzed genomic profiles of 3,732 cancer patients in whom several tumor sites were longitudinally biopsied. During distant metastasis, tumors were observed to accumulate copy number alterations (CNAs) to a much greater degree than mutations. In particular, the development of whole genome duplication was a common event during metastasis, emerging de novo in 28% of patients. Loss of 9p (including CDKN2A) developed during metastasis in 11% of patients. To a lesser degree, mutations and allelic loss in human leukocyte antigen class I and other genes associated with antigen presentation also emerged. Increasing CNA, but not increasing mutational load, was associated with immune evasion in patients treated with immunotherapy. Taken together, these data suggest that CNA, rather than mutational accumulation, is enriched during cancer metastasis, perhaps due to a more favorable balance of enhanced cellular fitness versus immunogenicity.
