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

作者：Serizawa Masakuni; Koh Yasuhiro^*; Kenmotsu Hirotsugu; Isaka Mitsuhiro; Murakami Haruyasu; Akamatsu Hiroaki; Mori Keita; Abe Masato; Hayashi Isamu; Taira Tetsuhiko; Maniwa Tomohiro; Takahashi Toshiaki; Endo Masahiro; Nakajima Takashi; Ohde Yasuhisa; Yamamoto Nobuyuki

来源：Cancer, 2014, 120(10): 1471-1481.

DOI：10.1002/cncr.28604

• lung adenocarcinoma
• driver mutation
• multimutational profiling
• molecular-targeted therapeutics
• personalized cancer medicine

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.

• 出版日期2014-5-15