Genomic rearrangements define lineage relationships between adjacent lepidic and invasive components in lung adenocarcinoma

Stephen J. Murphy, Dennis A. Wigle, Joema Felipe Lima, Faye R. Harris, Sarah H. Johnson, Geoffrey Halling, Michael K. Asiedu, Charlie T. Seto, Simone Terra, Farhad Kosari, Tobias Peikert, Ping Yang, Marie Christine Aubry, George Vasmatzis

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


The development of adenocarcinoma of the lung is believed to proceed from in situ disease (adenocarcinoma in situ, AIS) to minimally invasive disease with prominent lepidic growth (minimally invasive adenocarcinoma, MIA), then to fully invasive adenocarcinoma (AD), but direct evidence for this model has been lacking. Because some lung adenocarcinomas show prominent lepidic growth (AD-L), we designed a study to address the lineage relationship between the lepidic (noninvasive) component (L) and the adjacent nonlepidic growth component representing invasive disease within individual tumors. Lineage relationships were evaluated by next-generation DNA sequencing to define large genomic rearrangements in microdissected tissue specimens collected by laser capture. We found a strong lineage relationship between the majority of adjacent lepidic and invasive components, supporting a putative AIS-AD transition. Notably, many rearrangements were detected in the less aggressive lepidic component, although the invasive component exhibited an overall higher rate of genomic rearrangement. Furthermore, a significant number of genomic rearrangements were present in histologically normal lung adjacent to tumor, but not in host germline DNA, suggesting field defects restricted to zonal regions near a tumor. Our results offer a perspective on the genetic pathogenesis underlying adenocarcinoma development and its clinical management.

Original languageEnglish (US)
Pages (from-to)3157-3167
Number of pages11
JournalCancer research
Issue number11
StatePublished - Jun 1 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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