干旱区生态环境知识资源中心(Arid): Nongenetic Evolution Drives Lung Adenocarcinoma Spatial Heterogeneity and Progression

Arid

DOI	10.1158/2159-8290.CD-20-1274
	Nongenetic Evolution Drives Lung Adenocarcinoma Spatial Heterogeneity and Progression
	Tavernari, Daniele; Battistello, Elena; Dheilly, Elie; Petruzzella, Aaron S.; Mina, Marco; Sordet-Dessimoz, Jessica; Peters, Solange; Krueger, Thorsten; Gfeller, David; Riggi, Nicolo; Oricchio, Elisa; Letovanec, Igor; Ciriello, Giovanni
通讯作者	Ciriello, G (corresponding author), Univ Lausanne, Dept Computat Biol, CH-1015 Lausanne, Switzerland. ; Letovanec, I (corresponding author), Hop Valais, Ave Grand Champsec 80, CH-1951 Sion, Switzerland.
来源期刊	CANCER DISCOVERY
ISSN	2159-8274
EISSN	2159-8290
出版年	2021
卷号	11 期号:6 页码:1490-1507
英文摘要	Cancer evolution determines molecular and morphologic intratumor heterogeneity and challenges the design of effective treatments. In lung adenocarcinoma, disease progression and prognosis are associated with the appearance of morphologically diverse tumor regions, termed histologic patterns. However, the link between molecular and histologic features remains elusive. Here, we generated multiomics and spatially resolved molecular profiles of histologic patterns from primary lung adenocarcinoma, which we integrated with molecular data from >2,000 patients. The transition from indolent to aggressive patterns was not driven by genetic alterations but by epigenetic and transcriptional reprogramming reshaping cancer cell identity. A signature quantifying this transition was an independent predictor of patient prognosis in multiple human cohorts. Within individual tumors, highly multiplexed protein spatial profiling revealed coexistence of immune desert, inflamed, and excluded regions, which matched histologic pattern composition. Our results provide a detailed molecular map of lung adenocarcinoma intratumor spatial heterogeneity, tracing nongenetic routes of cancer evolution. SIGNIFICANCE: Lung adenocarcinomas are classified based on histologic pattern prevalence. However, individual tumors exhibit multiple patterns with unknown molecular features. We characterized nongenetic mechanisms underlying intratumor patterns and molecular markers predicting patient prognosis. Intratumor patterns determined diverse immune microenvironments, warranting their study in the context of current immunotherapies.
类型	Article
语种	英语
开放获取类型	Bronze
收录类别	SCI-E
WOS记录号	WOS:000659290300032
WOS关键词	TUMOR-SUPPRESSOR GENE ; BIOCONDUCTOR PACKAGE ; SOMATIC MUTATIONS ; NEVER SMOKERS ; MOUSE MODELS ; EARLY-STAGE ; OPEN-LABEL ; CANCER ; EXPRESSION ; IMMUNOTHERAPY
WOS类目	Oncology
WOS研究方向	Oncology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/349777
作者单位	[Tavernari, Daniele; Battistello, Elena; Dheilly, Elie; Petruzzella, Aaron S.; Mina, Marco; Peters, Solange; Gfeller, David; Riggi, Nicolo; Oricchio, Elisa; Letovanec, Igor; Ciriello, Giovanni] Swiss Canc Ctr Leman, Lausanne, Switzerland; [Tavernari, Daniele; Battistello, Elena; Mina, Marco; Ciriello, Giovanni] Univ Lausanne UNIL, Dept Comp Biol, Lausanne, Switzerland; [Tavernari, Daniele; Battistello, Elena; Mina, Marco; Ciriello, Giovanni] Swiss Inst Bioinformat, Lausanne, Switzerland; [Battistello, Elena; Dheilly, Elie; Petruzzella, Aaron S.; Sordet-Dessimoz, Jessica; Oricchio, Elisa] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res ISREC, Lausanne, Switzerland; [Peters, Solange] Univ Hosp Lausanne CHUV, Dept Oncol, Lausanne, Switzerland; [Krueger, Thorsten] Univ Hosp Lausanne CHUV, Div Thorac Surg, Lausanne, Switzerland; [Gfeller, David] Univ Lausanne UNIL, Ludwig Inst Canc Res, Dept Oncol, Lausanne, Switzerland; [Riggi, Nicolo; Letovanec, Igor] Univ Hosp Lausanne CHUV, Inst Pathol, Lausanne, Swi...
推荐引用方式 GB/T 7714	Tavernari, Daniele,Battistello, Elena,Dheilly, Elie,et al. Nongenetic Evolution Drives Lung Adenocarcinoma Spatial Heterogeneity and Progression[J],2021,11(6):1490-1507.
APA	Tavernari, Daniele.,Battistello, Elena.,Dheilly, Elie.,Petruzzella, Aaron S..,Mina, Marco.,...&Ciriello, Giovanni.(2021).Nongenetic Evolution Drives Lung Adenocarcinoma Spatial Heterogeneity and Progression.CANCER DISCOVERY,11(6),1490-1507.
MLA	Tavernari, Daniele,et al."Nongenetic Evolution Drives Lung Adenocarcinoma Spatial Heterogeneity and Progression".CANCER DISCOVERY 11.6(2021):1490-1507.