Nongenetic Evolution Drives Lung Adenocarcinoma Spatial Heterogeneity and Progression.

Details

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State: Public
Version: Author's accepted manuscript
License: Not specified
Serval ID
serval:BIB_F6D4BAEDCE1E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Nongenetic Evolution Drives Lung Adenocarcinoma Spatial Heterogeneity and Progression.
Journal
Cancer discovery
Author(s)
Tavernari D., Battistello E., Dheilly E., Petruzzella A.S., Mina M., Sordet-Dessimoz J., Peters S., Krueger T., Gfeller D., Riggi N., Oricchio E., Letovanec I., Ciriello G.
ISSN
2159-8290 (Electronic)
ISSN-L
2159-8274
Publication state
Published
Issued date
06/2021
Peer-reviewed
Oui
Volume
11
Number
6
Pages
1490-1507
Language
english
Notes
Publication types: Journal Article ; Comment
Publication Status: ppublish
Abstract
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.This article is highlighted in the In This Issue feature, p. 1307.
Pubmed
Web of science
Open Access
Yes
Create date
22/02/2021 14:41
Last modification date
03/07/2021 6:32
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