Assessment of Mutational Profile of Japanese Lung Adenocarcinoma Patients by Multitarget Assays

被引：58

作者：

Serizawa, Masakuni ^{[1
,2
]}

Koh, Yasuhiro ^{[2
]}

Kenmotsu, Hirotsugu ^{[1
]}

Isaka, Mitsuhiro ^{[3
]}

Murakami, Haruyasu ^{[1
]}

Akamatsu, Hiroaki ^{[1
,4
]}

Mori, Keita ^{[5
]}

Abe, Masato ^{[6
]}

Hayashi, Isamu ^{[6
]}

Taira, Tetsuhiko ^{[1
]}

Maniwa, Tomohiro ^{[3
]}

Takahashi, Toshiaki ^{[1
]}

Endo, Masahiro ^{[7
]}

Nakajima, Takashi ^{[6
]}

Ohde, Yasuhisa ^{[3
]}

Yamamoto, Nobuyuki ^{[1
,4
]}

机构：

[1] Shizuoka Canc Ctr, Div Thorac Oncol, Shizuoka, Japan

[2] Shizuoka Canc Ctr, Drug Discovery & Dev Div, Res Inst, Nagaizumi, Shizuoka 4118777, Japan

[3] Shizuoka Canc Ctr, Div Thorac Surg, Shizuoka, Japan

[4] Wakayama Med Univ, Dept Internal Med 3, Wakayama, Japan

[5] Shizuoka Canc Ctr, Clin Trial Coordinat Off, Shizuoka, Japan

[6] Shizuoka Canc Ctr, Div Pathol, Shizuoka, Japan

[7] Shizuoka Canc Ctr, Div Diagnost Radiol, Shizuoka, Japan

来源：

CANCER | 2014年 / 120卷 / 10期

关键词：

lung adenocarcinoma; driver mutation; multimutational profiling; molecular-targeted therapeutics; personalized cancer medicine; DRIVER MUTATIONS; CANCER; REARRANGEMENT; COEXISTENCE; SMOKERS; TARGETS; NSCLC; EGFR;

D O I：

10.1002/cncr.28604

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUNDIntegration of mutational profiling to identify driver genetic alterations in a clinical setting is necessary to facilitate personalized lung cancer medicine. A tumor genotyping panel was developed and the Shizuoka Lung Cancer Mutation Study was initiated as a prospective tumor genotyping study. This study reports the frequency of driver genetic alterations in Japanese lung adenocarcinoma patients, and clinicopathologic correlations with each genotype. METHODSBetween July 2011 and January 2013, 411 lung adenocarcinoma patients admitted to the Shizuoka Cancer Center were included in this study with their written informed consent. Surgically resected tissues, tumor biopsies, and/or body cavity fluids were collected and tested for 23 hotspot sites of driver mutations in 9 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2), gene amplifications in 5 genes (EGFR, MET, PIK3CA, FGFR1, and FGFR2), and ALK, ROS1, and RET fusions. RESULTSGenetic alterations were detected in 54.3% (223 of 411) of all patients. The most common genetic alterations detected in this study were EGFR mutations (35.0%) followed by KRAS mutations (8.5%) and ALK fusions (5.0%). Concurrent genetic alterations were detected in 22 patients (5.4%), and EGFR mutations were observed in 16 patients as the most common partner for concurrent genetic alteration. Significantly more concurrent genetic alterations were observed in older patients. CONCLUSIONSThis is one of the largest reports of a prospective tumor genotyping study on Japanese patients with adenocarcinoma. These data suggest that mutational profiling data using a multimutational testing platform would be valuable for expanding the range of molecular-targeted therapeutics in lung cancer. Cancer 2014;120:1471-1481. (c) 2014 American Cancer Society. This prospective tumor genotyping study reveals the frequencies of driver mutations and clinicopathologic correlations with each genotype in 411 Japanese lung adenocarcinoma patients. This study also highlights the importance of incorporating multimutational testing in the clinic.

引用

页码：1471 / 1481

页数：11

共 27 条

[1] The Introduction of Systematic Genomic Testing for Patients with Non-Small-Cell Lung Cancer [J].

Cardarella, Stephanie ;

Ortiz, Taylor M. ;

Joshi, Victoria A. ;

Butaney, Mohit ;

Jackman, David M. ;

Kwiatkowski, David J. ;

Yeap, Beow Y. ;

Jaenne, Pasi A. ;

Lindeman, Neal I. ;

Johnson, Bruce E. .

JOURNAL OF THORACIC ONCOLOGY, 2012, 7 (12) :1767-1774

[2] Coexistence of PIK3CA and Other Oncogene Mutations in Lung Adenocarcinoma-Rationale for Comprehensive Mutation Profiling [J].

Chaft, Jamie E. ;

Arcila, Maria E. ;

Paik, Paul K. ;

Lau, Christopher ;

Riely, Gregory J. ;

Pietanza, M. Catherine ;

Zakowski, Maureen F. ;

Rusch, Valerie ;

Sima, Camelia S. ;

Ladanyi, Marc ;

Kris, Mark G. .

MOLECULAR CANCER THERAPEUTICS, 2012, 11 (02) :485-491

[3] Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu [J].

De Greve, J. ;

Teugels, E. ;

Geers, C. ;

Decoster, L. ;

Galdermans, D. ;

De Mey, J. ;

Everaert, H. ;

Umelo, I. ;

In't Veld, P. ;

Schallier, D. .

LUNG CANCER, 2012, 76 (01) :123-127

[4] New Targets in Non-Small Cell Lung Cancer [J].

Gadgeel, Shirish M. .

CURRENT ONCOLOGY REPORTS, 2013, 15 (04) :411-423

[5] A Patient With BRAF V600E Lung Adenocarcinoma Responding to Vemurafenib [J].

Gautschi, Oliver ;

Pauli, Chantal ;

Strobel, Klaus ;

Hirschmann, Astrid ;

Printzen, Gert ;

Aebi, Stefan ;

Diebold, Joachim .

JOURNAL OF THORACIC ONCOLOGY, 2012, 7 (10) :E23-E24

[6] Introduction [J].

Johnson, Bruce ;

Cloonan, Martin .

[7] KIF5B-RET fusions in lung adenocarcinoma [J].

Kohno, Takashi ;

Ichikawa, Hitoshi ;

Totoki, Yasushi ;

Yasuda, Kazuki ;

Hiramoto, Masaki ;

Nammo, Takao ;

Sakamoto, Hiromi ;

Tsuta, Koji ;

Furuta, Koh ;

Shimada, Yoko ;

Iwakawa, Reika ;

Ogiwara, Hideaki ;

Oike, Takahiro ;

Enari, Masato ;

Schetter, Aaron J. ;

Okayama, Hirokazu ;

Haugen, Aage ;

Skaug, Vidar ;

Chiku, Suenori ;

Yamanaka, Itaru ;

Arai, Yasuhito ;

Watanabe, Shun-ichi ;

Sekine, Ikuo ;

Ogawa, Seishi ;

Harris, Curtis C. ;

Tsuda, Hitoshi ;

Yoshida, Teruhiko ;

Yokota, Jun ;

Shibata, Tatsuhiro .

NATURE MEDICINE, 2012, 18 (03) :375-377

[8] Anaplastic Lymphoma Kinase Inhibition in Non-Small-Cell Lung Cancer [J].

Kwak, Eunice L. ;

Bang, Yung-Jue ;

Camidge, D. Ross ;

Shaw, Alice T. ;

Solomon, Benjamin ;

Maki, Robert G. ;

Ou, Sai-Hong I. ;

Dezube, Bruce J. ;

Jaenne, Pasi A. ;

Costa, Daniel B. ;

Varella-Garcia, Marileila ;

Kim, Woo-Ho ;

Lynch, Thomas J. ;

Fidias, Panos ;

Stubbs, Hannah ;

Engelman, Jeffrey A. ;

Sequist, Lecia V. ;

Tan, WeiWei ;

Gandhi, Leena ;

Mino-Kenudson, Mari ;

Wei, Greg C. ;

Shreeve, S. Martin ;

Ratain, Mark J. ;

Settleman, Jeffrey ;

Christensen, James G. ;

Haber, Daniel A. ;

Wilner, Keith ;

Salgia, Ravi ;

Shapiro, Geoffrey I. ;

Clark, Jeffrey W. ;

Iafrate, A. John .

NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (18) :1693-1703

[9] Spectrum of Oncogenic Driver Mutations in Lung Adenocarcinomas from East Asian Never Smokers [J].

Li, Chenguang ;

Fang, Rong ;

Sun, Yihua ;

Han, Xiangkun ;

Li, Fei ;

Gao, Bin ;

Iafrate, A. John ;

Liu, Xin-Yuan ;

Pao, William ;

Chen, Haiquan ;

Ji, Hongbin .

PLOS ONE, 2011, 6 (11)

[10] Frequency of well-identified oncogenic driver mutations in lung adenocarcinoma of smokers varies with histological subtypes and graduated smoking dose [J].

Li, Hang ;

Pan, Yunjian ;

Li, Yuan ;

Li, Chenguang ;

Wang, Rui ;

Hu, Haichuan ;

Zhang, Yang ;

Ye, Ting ;

Wang, Lei ;

Shen, Lei ;

Sun, Yihua ;

Chen, Haiquan .

LUNG CANCER, 2013, 79 (01) :8-13

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