|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Kim, Y, Hammerman, PS, Kim, J, Yoon, J-ae, Lee, Y, Sun, J-M, Wilkerson, MD, Pedamallu, CSekhar, Cibulskis, K, Yoo, YKyung, Lawrence, MS, Stojanov, P, Carter, SL, McKenna, A, Stewart, C, Sivachenko, AY, Oh, I-J, Kim, HKwan, Choi, YSoo, Kim, K, Shim, YMog, Kim, K-S, Song, S-Y, Na, K-J, La Choi, Y-, D Hayes, N, Kim, J, Cho, S, Kim, Y-C, Ahn, JSeok, Ahn, M-J, Getz, G, Meyerson, M, Park, K|
|Journal||J Clin Oncol|
|Date Published||2014 Jan 10|
|Keywords||Adult, Aged, Aged, 80 and over, Asian Continental Ancestry Group, Carcinoma, Squamous Cell, DNA-Binding Proteins, European Continental Ancestry Group, Female, Gene Expression Regulation, Neoplastic, Humans, Intracellular Signaling Peptides and Proteins, Kelch-Like ECH-Associated Protein 1, Lung Neoplasms, Male, Middle Aged, Models, Genetic, Mutation, Neoplasm Proteins, NF-E2-Related Factor 2, Phosphatidylinositol 3-Kinases, PTEN Phosphohydrolase, Republic of Korea, Retinoblastoma Protein, Smoking, Transcriptome, Tumor Suppressor Protein p53, United States|
PURPOSE: Lung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients.
PATIENTS AND METHODS: We performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated.
RESULTS: This cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC.
CONCLUSION: These findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.
|Alternate Journal||J. Clin. Oncol.|
|PubMed Central ID||PMC4062710|
|Grant List||K08 CA163677 / CA / NCI NIH HHS / United States|