Assessment of mutational profile of Japanese lung adenocarcinoma patients by multitarget assays: a prospective, single-institute study.
BACKGROUND
Integration 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.


METHODS
Between 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.


RESULTS
Genetic 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.


CONCLUSIONS
This 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.
Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan; Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
Masakuni
M
Serizawa
Yasuhiro
Y
Koh
Hirotsugu
H
Kenmotsu
Mitsuhiro
M
Isaka
Haruyasu
H
Murakami
Hiroaki
H
Akamatsu
Keita
K
Mori
Masato
M
Abe
Isamu
I
Hayashi
Tetsuhiko
T
Taira
Tomohiro
T
Maniwa
Toshiaki
T
Takahashi
Masahiro
M
Endo
Takashi
T
Nakajima
Yasuhisa
Y
Ohde
Nobuyuki
N
Yamamoto
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D044466:Asian People / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
driver mutation; lung adenocarcinoma; molecular-targeted therapeutics; multimutational profiling; personalized cancer medicine