Genomic Landscape of Atypical Adenomatous Hyperplasia Reveals Divergent Modes to Lung Adenocarcinoma

There is a dearth of knowledge about the pathogenesis of premalignant lung lesions, especially for atypical adenomatous hyperplasia (AAH), the only known precursor for the major lung cancer subtype adenocarcinoma (LUAD). In this study, we performed deep DNA and RNA sequencing analyses of a set of AA...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cancer research (Chicago, Ill.) Jg. 77; H. 22; S. 6119
Hauptverfasser: Sivakumar, Smruthy, Lucas, F Anthony San, McDowell, Tina L, Lang, Wenhua, Xu, Li, Fujimoto, Junya, Zhang, Jianjun, Futreal, P Andrew, Fukuoka, Junya, Yatabe, Yasushi, Dubinett, Steven M, Spira, Avrum E, Fowler, Jerry, Hawk, Ernest T, Wistuba, Ignacio I, Scheet, Paul, Kadara, Humam
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 15.11.2017
Schlagworte:
Adenocarcinoma - genetics
Adenocarcinoma - pathology
Aged
Disease Progression
Female
Gene Expression Profiling
Genomics
Humans
Hyperplasia - genetics
Lung - metabolism
Lung - pathology
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Male
Middle Aged
Mutation
Precancerous Conditions - genetics
Proto-Oncogene Proteins B-raf - genetics
Proto-Oncogene Proteins p21(ras) - genetics
ISSN:1538-7445, 1538-7445
Online-Zugang:Weitere Angaben
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:There is a dearth of knowledge about the pathogenesis of premalignant lung lesions, especially for atypical adenomatous hyperplasia (AAH), the only known precursor for the major lung cancer subtype adenocarcinoma (LUAD). In this study, we performed deep DNA and RNA sequencing analyses of a set of AAH, LUAD, and normal tissues. Somatic variants were found in AAHs from 5 of 22 (23%) patients, 4 of 5 of whom had matched LUAD with driver mutations. mutations were present in AAHs from 4 of 22 (18%) of patients. mutations in AAH were only found in ever-smokers and were exclusive to -mutant cases. Integrative analysis revealed profiles expressed in -mutant cases ( ) and -mutant cases ( ) of AAH, or common to both sets of cases (suppressed ). Gene sets associated with suppressed antitumor (Th1; ) and elevated protumor ( ) immune signaling were enriched in AAH development and progression. Our results reveal potentially divergent or pathways in AAH as well as immune dysregulation in the pathogenesis of this premalignant lung lesion. .
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1538-7445
1538-7445
DOI:10.1158/0008-5472.CAN-17-1605