Abstract:
:Lungs resected for adenocarcinomas often harbour minute discrete foci of cytologically atypical pneumocyte proliferations designated as atypical adenomatous hyperplasia (AAH). Evidence suggests that AAH represents an initial step in the progression to adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and fully invasive adenocarcinoma. Despite efforts to identify predictive markers of malignant transformation, alterations driving this progression are poorly understood. Here we perform targeted next-generation sequencing on multifocal AAHs and different zones of histologic progression within AISs and MIAs. Multiregion sequencing demonstrated different genetic drivers within the same tumour and reveal that clonal expansion is an early event of tumorigenesis. We find that KRAS, TP53 and EGFR mutations are indicators of malignant transition. Utilizing droplet digital PCR, we find alterations associated with early neoplasms in paired circulating DNA. This study provides insight into the heterogeneity of clonal events in the progression of early lung neoplasia and demonstrates that these events can be detected even before neoplasms have invaded and acquired malignant potential.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Izumchenko E,Chang X,Brait M,Fertig E,Kagohara LT,Bedi A,Marchionni L,Agrawal N,Ravi R,Jones S,Hoque MO,Westra WH,Sidransky Ddoi
10.1038/ncomms9258subject
Has Abstractpub_date
2015-09-16 00:00:00pages
8258issn
2041-1723pii
ncomms9258journal_volume
6pub_type
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