Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA.

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 Commun

journal_title

Nature communications

authors

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 D

doi

10.1038/ncomms9258

subject

Has Abstract

pub_date

2015-09-16 00:00:00

pages

8258

issn

2041-1723

pii

ncomms9258

journal_volume

6

pub_type

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