Genomics of lung cancer

Abstract

This review focuses on recent research using genomics to examine lung carcinogenesis, histologic differentiation, and progression.

Figure 1.

Comparison of gene expression of human lung tumors with genes temporally expressed during lung development suggests a recapitulation of developmentally regulated pathways. Nearest neighbor analysis was used to classify and rank murine (Mu11k) gene markers associated with two groups associated with lung development stage. Each row in the heat map (middle panel) shows gene expression over time for murine genes. Lung development stages represented by Group 1 (Days E12–E18, top panel) and Group 2 (Postnatal Day 1–Adult, lower panel) highly expressed genes are pseudoglandular/canalicular and terminal sac/alveolar, respectively. The corresponding human histology gene orthologs for large cell carcinoma are indicated in red, adenocarcinoma in blue. Specifically, genes expressed by large cell carcinoma mirror those expressed during the early pseudoglandular and canalicular stages of lung development, while those expressed by adenocarcinoma are predominantly expressed during the later terminal sac and alveolar stages.

Figure 2.

Classification of lung adenocarcinoma reflects progression along a spectrum of invasiveness spanning epithelial atypia, bronchioloalveolar adenocarcinoma (BAC), BAC with foci of microinvasion, and invasive adenocarcinoma. In cells with repression of TGFβ-RII (lower panel), signaling through the Smad pathway is abrogated (right). Invasiveness is mediated through noncanonical signaling pathways that require RANTES (left).