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...

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Published in:Cancer research (Chicago, Ill.) Vol. 77; no. 22; p. 6119
Main Authors: 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
Language:English
Published: United States 15.11.2017
Subjects:
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 Access:Get more information
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Summary: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. .
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ISSN:1538-7445
1538-7445
DOI:10.1158/0008-5472.CAN-17-1605