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J Clin Oncol. 2014 Jan 10;32(2):121-8. doi: 10.1200/JCO.2013.50.8556. Epub 2013 Dec 9.

Integrative and comparative genomic analysis of lung squamous cell carcinomas in East Asian patients.

Author information

1
Youngwook Kim, Ji-ae Yoon, Yoomi Lee, Yeong Kyung Yoo, and Keunchil Park, Samsung Medical Center, Samsung Biomedical Research Institute; Jong-Mu Sun, Hong Kwan Kim, Yong Soo Choi, Kwhanmien Kim, Young Mog Shim, Yoon-La Choi, Jhingook Kim, Jin Seok Ahn, Myung-Ju Ahn, and Keunchil Park, Samsung Medical Center, Sungkyunkwan University School of Medicine; Sukki Cho, Seoul National University Bundang Hospital, College of Medicine, Seoul National University, Seoul; In-Jae Oh, Kyu-Sik Kim, Sang-Yun Song, Kook-Ju Na, and Young-Chul Kim, Chonnam National University Hwasun Hospital, Jeonnam, Republic of Korea; Peter S. Hammerman, Jaegil Kim, Chandra Sekhar Pedamallu, Kristian Cibulskis, Michael S. Lawrence, Petar Stojanov, Scott L. Carter, Aaron McKenna, Chip Stewart, Andrey Y. Sivachenko, Gad Getz, and Matthew Meyerson, Broad Institute of Harvard and MIT, Cambridge; Matthew Meyerson, Harvard Medical School; Peter S. Hammerman and Chandra Sekhar Pedamallu, Dana-Farber Cancer Institute; Gad Getz, Massachusetts General Hospital Cancer Center, Boston, MA; and Matthew D. Wilkerson and D. Neil Hayes, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Abstract

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.

PMID:
24323028
PMCID:
PMC4062710
DOI:
10.1200/JCO.2013.50.8556
[Indexed for MEDLINE]
Free PMC Article

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