title: Rewiring of human lung cell lineage and mitotic networks in lung adenocarcinomas.
abstract: Analysis of gene expression patterns in normal tissues and their perturbations in tumours can help to identify the functional roles of oncogenes or tumour suppressors and identify potential new therapeutic targets. Here, gene expression correlation networks were derived from 92 normal human lung samples and patient-matched adenocarcinomas. The networks from normal lung show that NKX2-1 is linked to the alveolar type 2 lineage, and identify PEBP4 as a novel marker expressed in alveolar type 2 cells. Differential correlation analysis shows that the NKX2-1 network in tumours includes pathways associated with glutamate metabolism, and identifies Vaccinia-related kinase (VRK1) as a potential drug target in a tumour-specific mitotic network. We show that VRK1 inhibition cooperates with inhibition of poly (ADP-ribose) polymerase signalling to inhibit growth of lung tumour cells. Targeting of genes that are recruited into tumour mitotic networks may provide a wider therapeutic window than that seen by inhibition of known mitotic genes.
authors.affiliation: Thoracic Oncology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, California 94115, USA.
authors.forename: Il-Jin
authors.initials: IJ
authors.lastname: Kim
authors.forename: David
authors.initials: D
authors.lastname: Quigley
authors.forename: Minh D
authors.initials: MD
authors.lastname: To
authors.forename: Patrick
authors.initials: P
authors.lastname: Pham
authors.forename: Kevin
authors.initials: K
authors.lastname: Lin
authors.forename: Brian
authors.initials: B
authors.lastname: Jo
authors.forename: Kuang-Yu
authors.initials: KY
authors.lastname: Jen
authors.forename: Dan
authors.initials: D
authors.lastname: Raz
authors.forename: Jae
authors.initials: J
authors.lastname: Kim
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Mao
authors.forename: David
authors.initials: D
authors.lastname: Jablons
authors.forename: Allan
authors.initials: A
authors.lastname: Balmain
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D019070:Cell Lineage; D020869:Gene Expression Profiling; D006801:Humans; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008938:Mitosis