Whole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma

Yasuhiko Haga, Yoshitaka Sakamoto, Keiko Kajiya, Hitomi Kawai, Miho Oka, Noriko Motoi, Masayuki Shirasawa, Masaya Yotsukura, Shun-Ichi Watanabe, Miyuki Arai, Junko Zenkoh, Kouya Shiraishi, Masahide Seki, Akinori Kanai, Yuichi Shiraishi, Yasushi Yatabe, Daisuke Matsubara, Yutaka Suzuki (), Masayuki Noguchi, Takashi Kohno () and Ayako Suzuki ()
Additional contact information
Yasuhiko Haga: The University of Tokyo
Yoshitaka Sakamoto: The University of Tokyo
Keiko Kajiya: The University of Tokyo
Hitomi Kawai: University of Tsukuba
Miho Oka: The University of Tokyo
Noriko Motoi: National Cancer Center Hospital
Masayuki Shirasawa: National Cancer Center Hospital
Masaya Yotsukura: National Cancer Center Hospital
Shun-Ichi Watanabe: National Cancer Center Hospital
Miyuki Arai: The University of Tokyo
Junko Zenkoh: The University of Tokyo
Kouya Shiraishi: National Cancer Center Research Institute
Masahide Seki: The University of Tokyo
Akinori Kanai: The University of Tokyo
Yuichi Shiraishi: National Cancer Center Research Institute
Yasushi Yatabe: National Cancer Center Hospital
Daisuke Matsubara: University of Tsukuba
Yutaka Suzuki: The University of Tokyo
Masayuki Noguchi: University of Tsukuba
Takashi Kohno: National Cancer Center Research Institute
Ayako Suzuki: The University of Tokyo

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract The mechanism underlying the development of tumors, particularly at early stages, still remains mostly elusive. Here, we report whole-genome long and short read sequencing analysis of 76 lung cancers, focusing on very early-stage lung adenocarcinomas such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma. The obtained data is further integrated with bulk and spatial transcriptomic data and epigenomic data. These analyses reveal key events in lung carcinogenesis. Minimal somatic mutations in pivotal driver mutations and essential proliferative factors are the only detectable somatic mutations in the very early-stage of AIS. These initial events are followed by copy number changes and global DNA hypomethylation. Particularly, drastic changes are initiated at the later AIS stage, i.e., in Noguchi type B tumors, wherein cancer cells are exposed to the surrounding microenvironment. This study sheds light on the pathogenesis of lung adenocarcinoma from integrated pathological and molecular viewpoints.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-43732-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43732-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-43732-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().