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| Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas | |
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; Chow, Chi-Wan5; Pham, Hoa H. N.12; Godoy, Myrna C. B.13; Carter, Brett W.13; Behrens, Carmen4,5; Zhang, Jianhua1 ; Antonoff, Mara B.14; Sepesi, Boris14; Lu, Yue2,3; Pass, Harvey, I15; Kadara, Humam5; Scheet, Paul16; Vaporciyan, Ara A.14; Heymach, John, V4; Wistuba, Ignacio I.4,5; Lee, J. Jack17; Futreal, P. Andrew1; Su, Dan18; Issa, Jean-Pierre J.19; Zhang, Jianjun1,4
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| 2021-01-29 | |
| Source Publication | NATURE COMMUNICATIONS
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| ISSN | 2041-1723 |
| Corresponding Author | Futreal, P. Andrew(afutreal@mdanderson.org) ; Su, Dan(sudan@zjcc.org.cn) ; Issa, Jean-Pierre J.(jpissa@coriell.org) ; Zhang, Jianjun(jzhang20@mdanderson.org) |
| Abstract | 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. |
| DOI | 10.1038/s41467-021-20907-z |
| WOS Keyword | INTRATUMOR HETEROGENEITY ; EPIGENETIC REGULATION ; METHYLATION ; CANCER ; HYPOMETHYLATION ; PROGRESSION ; ANNOTATION ; LANDSCAPE ; TUMORS ; CELLS |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | 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] |
| Funding Organization | 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 |
| WOS Research Area | Science & Technology - Other Topics |
| WOS Subject | Multidisciplinary Sciences |
| WOS ID | WOS:000684845600015 |
| Publisher | NATURE PORTFOLIO |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.hfcas.ac.cn:8080/handle/334002/124460 |
| Collection | 中国科学院合肥物质科学研究院 |
| Corresponding Author | Futreal, P. Andrew; Su, Dan; Issa, Jean-Pierre J.; Zhang, Jianjun |
| Affiliation | 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 11.Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Zhejiang Canc Res Inst, Hangzhou 310022, Peoples R China 12.Nagasaki Univ, Dept Pathol, Grad Sch Biomed Sci, Nagasaki 8528523, Japan 13.Univ Texas MD Anderson Canc Ctr, Dept Thorac Imaging, Houston, TX 77030 USA 14.Univ Texas MD Anderson Canc Ctr, Thorac & Cardiovasc Surg, Houston, TX 77030 USA 15.NYU, Dept Cardiothorac Surg, Langone Med Ctr, New York, NY 10016 USA 16.Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA 17.Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA 18.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Dept Pathol, Canc Hosp, Hangzhou 310022, Peoples R China 19.Coriell Inst Med Res, Camden, NJ 08103 USA |
| Recommended Citation 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). |
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