HFCAS OpenIR
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
2021-01-29
Source PublicationNATURE COMMUNICATIONS
ISSN2041-1723
Corresponding AuthorFutreal, P. Andrew(afutreal@mdanderson.org) ; Su, Dan(sudan@zjcc.org.cn) ; Issa, Jean-Pierre J.(jpissa@coriell.org) ; Zhang, Jianjun(jzhang20@mdanderson.org)
AbstractThe 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.
DOI10.1038/s41467-021-20907-z
WOS KeywordINTRATUMOR HETEROGENEITY ; EPIGENETIC REGULATION ; METHYLATION ; CANCER ; HYPOMETHYLATION ; PROGRESSION ; ANNOTATION ; LANDSCAPE ; TUMORS ; CELLS
Indexed BySCI
Language英语
Funding ProjectMD 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 OrganizationMD 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 AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000684845600015
PublisherNATURE PORTFOLIO
Citation statistics
Cited Times:8[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.hfcas.ac.cn:8080/handle/334002/124460
Collection中国科学院合肥物质科学研究院
Corresponding AuthorFutreal, P. Andrew; Su, Dan; Issa, Jean-Pierre J.; Zhang, Jianjun
Affiliation1.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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