Abstract B41: Consider the source: Normal lung expression classifies cancer histologies, subtypes, and mutations

Lung cancer9s pathogenesis from normal cell to metastatic disease involves vast and complex genetic alterations. However, a patient9s genetic alterations do not completely explain the pathogenic process, for tumors with the same alterations have different features and therapy responses. We hypothesized that differences in ancestral anatomical regions affect pathogenesis and as such would correlate with differences in cancer histology, subtype, and mutations. Anatomical distal and proximal region specimens from normal lungs were collected and assayed by Agilent 44K gene expression microarrays and immunohistochemistry (IHC). 271 surgically extracted lung cancers were assayed by gene expression, IHC, and gene sequencing for EGFR, KRAS, STK11, and TP53. Using the normal lung specimens, a novel classifier was created to assign cancers with an anatomical region using gene expression alone. Cancers classified as distal by gene expression were 84% adenocarcinoma, while 73% of those classified as proximal were squamous cell carcinoma (P