RET expression and detection of KIF5B/RET gene rearrangements in Japanese lung cancer.
RET encodes the tyrosine kinase receptor of growth factors belonging to the glial-derived neurotrophic factor family. Recently, RET gene rearrangements with N-terminal of KIF5B gene were identified in lung adenocarcinomas from large-scale sequencing. We investigated RET mRNA expression by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay using LightCycler, and KIF5B/RET gene rearrangements using newly established fluorescence in situ hybridization (FISH) analysis in surgically treated nonsmall cell lung cancer (NSCLC) cases. RET protein expression was also investigated by immunohistochemistry (IHC). This study included 157 surgically removed NSCLC cases for mRNA level analyses. The RET/β actin mRNA levels were not significantly different between lung cancer (6.359 ± 15.268) and adjacent normal lung tissues (8.205 ± 28.931, P = 0.6332). Tumor/normal (T/N) ratio of RET/β actin mRNA levels was not different within gender, stage, smoking status, and pathological subtypes. T/N ratio of RET/β actin mRNA levels was significantly higher in KIF5B/RET rearrangement samples (161.763 ± 123.488) than in wild-type samples (5.9013 ± 17.148, P = 0.044). Although RET IHC positivity was not perfectly correlated with KIF5B/RET arrangement, we have detected the KIF5B/RET rearrangements using FISH analysis. Thus, we have successfully introduced FISH for diagnosing KIF5B/RET positive lung adenocarcinoma. This method facilitates the molecular evaluation for RET fusions and could be applicable in clinical practice to detect lung cancer that may be responsive to RET inhibitors.
Department of Oncology, Immunology, and Surgery, Nagoya City University Graduate School of Medical Sciences Nagoya, Japan. hisasaki@med.nagoya-cu.ac.jp
Hidefumi
H
Sasaki
Shigeki
S
Shimizu
Yoichi
Y
Tani
Masahiko
M
Maekawa
Katsuhiro
K
Okuda
Keisuke
K
Yokota
Masayuki
M
Shitara
Yu
Y
Hikosaka
Satoru
S
Moriyama
Motoki
M
Yano
Yoshitaka
Y
Fujii
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D005260:Female; D015870:Gene Expression; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D016547:Kinesins / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014178:Translocation, Genetic
C488101:KIF5B protein, human; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; D016547:Kinesins
FISH; KIF5B/RET; RET expression; lung cancer