Non-genetic 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
Non-genetic 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. (co-last), Ciriello G.
ISSN
2159-8290 (Electronic)
ISSN-L
2159-8274
Publication state
Published
Issued date
09/02/2021
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Cancer evolution determines molecular and morphological intra-tumor 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 histological features remains elusive. Here, we generated multi-omics 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 co-existence of immune desert, inflamed, and excluded regions, which matched histologic pattern composition. Our results provide a detailed molecular map of lung adenocarcinoma intra-tumor spatial heterogeneity, tracing non-genetic routes of cancer evolution.
Pubmed
Open Access
Yes
Create date
22/02/2021 14:41
Last modification date
06/03/2021 7:23
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