{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360021391860875136.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1038/s41467-023-43732-y"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/s41467-023-43732-y.pdf"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/s41467-023-43732-y"}},{"identifier":{"@type":"PMID","@value":"38102134"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Whole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title><jats:p>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.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380021391860875151","@type":"Researcher","foaf:name":[{"@value":"Yasuhiko Haga"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391860875147","@type":"Researcher","foaf:name":[{"@value":"Yoshitaka Sakamoto"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391860875053","@type":"Researcher","foaf:name":[{"@value":"Keiko Kajiya"}]},{"@id":"https://cir.nii.ac.jp/crid/1420285329317355264","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"50895026"},{"@type":"NRID","@value":"1000050895026"}],"foaf:name":[{"@value":"Hitomi Kawai"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391860874881","@type":"Researcher","foaf:name":[{"@value":"Miho Oka"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391860875137","@type":"Researcher","foaf:name":[{"@value":"Noriko 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resolution mapping of the breast cancer tumor microenvironment using integrated single cell, spatial and in situ analysis of FFPE tissue"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588380132401280","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Spatially resolved gene expression profiling of tumor microenvironment reveals key steps of lung adenocarcinoma development"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846641728589824","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"International network of cancer genome projects"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846642536063104","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Aberrant transcriptional regulations in cancers: genome, transcriptome and epigenome analysis of lung adenocarcinoma cell 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