title: Comprehensive genomic analyses of a metastatic colon cancer to the lung by whole exome sequencing and gene expression analysis.
abstract: We performed whole exome sequencing and gene expression analysis on a metastatic colon cancer to the lung, along with the adjacent normal tissue of the lung. Whole exome sequencing uncovered 71 high-confidence non‑synonymous mutations. We selected 16 mutation candidates, and 13 out of 16 mutations were validated by targeted deep sequencing using the Ion Torrent PGM customized AmpliSeq panel. By integrating mutation, copy number and gene expression microarray data, we identified a JAZF1 mutation with a gain-of-copy, suggesting its oncogenic potential for the lung metastasis from colon cancer. Our pathway analyses showed that the identified mutations closely reflected characteristics of the metastatic site (lung) while mRNA gene expression patterns kept genetic information of its primary tumor (colon). The most significant gene expression network was the 'Colorectal Cancer Metastasis Signaling', containing 6 (ADCY2, ADCY9, APC, GNB5, K-ras and LRP6) out of the 71 mutated genes. Some of these mutated genes (ADCY9, ADCY2, GNB5, K-ras, HDAC6 and ARHGEF17) also belong to the 'Phospholipase C Signaling' network, which suggests that this pathway and its mutated genes may contribute to a lung metastasis from colon cancer.
authors.affiliation: Thoracic Oncology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Li Tai
authors.initials: LT
authors.lastname: Fang
authors.forename: Sharon
authors.initials: S
authors.lastname: Lee
authors.forename: Helen
authors.initials: H
authors.lastname: Choi
authors.forename: Hong Kwan
authors.initials: HK
authors.lastname: Kim
authors.forename: Gregory
authors.initials: G
authors.lastname: Jew
authors.forename: Hio Chung
authors.initials: HC
authors.lastname: Kang
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Jablons
authors.forename: Il-Jin
authors.initials: IJ
authors.lastname: Kim
mesh_terms: D000368:Aged; D056970:Co-Repressor Proteins; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins; D059472:Exome; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C430460:JAZF1 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger