Integrative and Comparative Genomic Analysis of Lung Squamous Cell Carcinomas in East Asian Patients

被引：172

作者：

Kim, Youngwook ^{[1
]}

Hammerman, Peter S. ^{[5
,7
]}

Kim, Jaegil ^{[5
]}

Yoon, Ji-ae ^{[1
]}

Lee, Yoomi ^{[1
]}

Sun, Jong-Mu ^{[2
]}

Wilkerson, Matthew D. ^{[9
]}

Pedamallu, Chandra Sekhar ^{[5
,7
]}

Cibulskis, Kristian ^{[5
]}

Yoo, Yeong Kyung ^{[1
]}

Lawrence, Michael S. ^{[5
]}

Stojanov, Petar ^{[5
]}

Carter, Scott L. ^{[5
]}

McKenna, Aaron ^{[5
]}

Stewart, Chip ^{[5
]}

Sivachenko, Andrey Y. ^{[5
]}

Oh, In-Jae ^{[4
]}

Kim, Hong Kwan ^{[2
]}

Choi, Yong Soo ^{[2
]}

Kim, Kwhanmien ^{[2
]}

Shim, Young Mog ^{[2
]}

Kim, Kyu-Sik ^{[4
]}

Song, Sang-Yun ^{[4
]}

Na, Kook-Joo ^{[4
]}

Choi, Yoon-La ^{[2
]}

Hayes, D. Neil ^{[9
]}

Kim, Jhingook ^{[2
]}

Cho, Sukki ^{[3
]}

Kim, Young-Chul ^{[4
]}

Ahn, Jin Seok ^{[2
]}

Ahn, Myung-Ju ^{[2
]}

Getz, Gad ^{[5
,8
]}

Meyerson, Matthew ^{[5
,6
]}

Park, Keunchil ^{[1
,2
]}

机构：

[1] Samsung Biomed Res Inst, Samsung Med Ctr, Seoul, South Korea

[2] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul 135710, South Korea

[3] Seoul Natl Univ, Coll Med, Bundang Hosp, Seoul, South Korea

[4] Chonnam Natl Univ, Hwasun Hosp, Jeonnam, South Korea

[5] Broad Inst Harvard & MIT, Cambridge, MA USA

[6] Harvard Univ, Sch Med, Boston, MA USA

[7] Dana Farber Canc Inst, Boston, MA 02115 USA

[8] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA

[9] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2014年 / 32卷 / 02期

关键词：

GROWTH-FACTOR RECEPTOR; HUMAN CANCERS; GENE FUSIONS; MUTATIONS; GEFITINIB; ADENOCARCINOMA; EGFR; IDENTIFICATION; AMPLIFICATION; GLIOBLASTOMA;

D O I：

10.1200/JCO.2013.50.8556

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：121 / +

页数：9

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