Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas
文献类型：期刊论文
| 作者 | Hu, Xin1; Estecio, Marcos R.2,3; Chen, Runzhe4; Reuben, Alexandre4; Wang, Linghua1; Fujimoto, Junya5; Carrot-Zhang, Jian6,7,8; McGranahan, Nicholas9; Ying, Lisha10,11; Fukuoka, Junya12 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2021-01-29 |
| 卷号 | 12 |
| ISSN号 | 2041-1723 |
| DOI | 10.1038/s41467-021-20907-z |
| 通讯作者 | Futreal, P. Andrew(afutreal@mdanderson.org) ; Su, Dan(sudan@zjcc.org.cn) ; Issa, Jean-Pierre J.(jpissa@coriell.org) ; Zhang, Jianjun(jzhang20@mdanderson.org) |
| 英文摘要 | The evolution of DNA methylome and methylation intra-tumor heterogeneity (ITH) during early carcinogenesis of lung adenocarcinoma has not been systematically studied. We perform reduced representation bisulfite sequencing of invasive lung adenocarcinoma and its precursors, atypical adenomatous hyperplasia, adenocarcinoma in situ and minimally invasive adenocarcinoma. We observe gradual increase of methylation aberrations and significantly higher level of methylation ITH in later-stage lesions. The phylogenetic patterns inferred from methylation aberrations resemble those based on somatic mutations suggesting parallel methylation and genetic evolution. De-convolution reveal higher ratio of T regulatory cells (Tregs) versus CD8+T cells in later-stage diseases, implying progressive immunosuppression with neoplastic progression. Furthermore, increased global hypomethylation is associated with higher mutation burden, copy number variation burden and AI burden as well as higher Treg/CD8 ratio, highlighting the potential impact of methylation on chromosomal instability, mutagenesis and tumor immune microenvironment during early carcinogenesis of lung adenocarcinomas. It is known that invasive lung adenocarcinomas evolve from pre-cancerous dysplastic lesions. In this study, the authors show that evolution of pre-cancerous lesions is accompanied by DNA methylation alterations, and that global hypomethylation correlates with immune infiltration, mutational burden and copy number alterations. |
| WOS关键词 | INTRATUMOR HETEROGENEITY ; EPIGENETIC REGULATION ; METHYLATION ; CANCER ; HYPOMETHYLATION ; PROGRESSION ; ANNOTATION ; LANDSCAPE ; TUMORS ; CELLS |
| 资助项目 | MD Anderson Khalifa Scholar Award ; National Cancer Institute of the National Institute of Health Research Project Grant[R01CA234629-01] ; AACR-Johnson & Johnson Lung Cancer Innovation Science Grant[18-90-52-ZHAN] ; MD Anderson Physician Scientist Program ; MD Anderson Lung Cancer Moon Shot Program ; Sabin Family Foundation Award ; Duncan Family Institute Cancer Prevention Research Seed Funding Program ; University of Texas MD Anderson Cancer Center Pre-Cancer Atlas Project, EDRN[U01CA214195] ; Cancer Prevention and Research Institute of Texas Multi-Investigator Research Award grant[RP160668] ; UT Lung Specialized Programs of Research Excellence Grant[P50CA70907] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| 出版者 | NATURE PORTFOLIO |
| WOS记录号 | WOS:000684845600015 |
| 资助机构 | MD Anderson Khalifa Scholar Award ; National Cancer Institute of the National Institute of Health Research Project Grant ; AACR-Johnson & Johnson Lung Cancer Innovation Science Grant ; MD Anderson Physician Scientist Program ; MD Anderson Lung Cancer Moon Shot Program ; Sabin Family Foundation Award ; Duncan Family Institute Cancer Prevention Research Seed Funding Program ; University of Texas MD Anderson Cancer Center Pre-Cancer Atlas Project, EDRN ; Cancer Prevention and Research Institute of Texas Multi-Investigator Research Award grant ; UT Lung Specialized Programs of Research Excellence Grant |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/124459]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Futreal, P. Andrew; Su, Dan; Issa, Jean-Pierre J.; Zhang, Jianjun |
| 作者单位 | 1.Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA 2.Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Houston, TX 77030 USA 3.Univ Texas MD Anderson Canc Ctr, Ctr Canc Epigenet, Houston, TX 77030 USA 4.Univ Texas MD Anderson Canc Ctr, Thorac Head & Neck Med Oncol, Houston, TX 77030 USA 5.Univ Texas MD Anderson Canc Ctr, Translat Mol Pathol, Houston, TX 77030 USA 6.Broad Inst MIT & Harvard, Cambridge, MA 02142 USA 7.Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA 8.Harvard Med Sch, Boston, MA 02115 USA 9.Canc Res United Kingdom Univ Coll London Lung Can, London SW7 3RP, England 10.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou 310022, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hu, Xin,Estecio, Marcos R.,Chen, Runzhe,et al. Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas[J]. NATURE COMMUNICATIONS,2021,12. |
| APA | Hu, Xin.,Estecio, Marcos R..,Chen, Runzhe.,Reuben, Alexandre.,Wang, Linghua.,...&Zhang, Jianjun.(2021).Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas.NATURE COMMUNICATIONS,12. |
| MLA | Hu, Xin,et al."Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas".NATURE COMMUNICATIONS 12(2021). |
入库方式： OAI收割
来源：合肥物质科学研究院
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。