PMID- 23342255 OWN - NLM STAT- MEDLINE DCOM- 20140117 LR - 20221207 IS - 2045-7634 (Print) IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 1 IP - 1 DP - 2012 Aug TI - RET expression and detection of KIF5B/RET gene rearrangements in Japanese lung cancer. PG - 68-75 LID - 10.1002/cam4.13 [doi] AB - 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/beta 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/beta actin mRNA levels was not different within gender, stage, smoking status, and pathological subtypes. T/N ratio of RET/beta 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. FAU - Sasaki, Hidefumi AU - Sasaki H AD - Department of Oncology, Immunology, and Surgery, Nagoya City University Graduate School of Medical Sciences Nagoya, Japan. hisasaki@med.nagoya-cu.ac.jp FAU - Shimizu, Shigeki AU - Shimizu S FAU - Tani, Yoichi AU - Tani Y FAU - Maekawa, Masahiko AU - Maekawa M FAU - Okuda, Katsuhiro AU - Okuda K FAU - Yokota, Keisuke AU - Yokota K FAU - Shitara, Masayuki AU - Shitara M FAU - Hikosaka, Yu AU - Hikosaka Y FAU - Moriyama, Satoru AU - Moriyama S FAU - Yano, Motoki AU - Yano M FAU - Fujii, Yoshitaka AU - Fujii Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120712 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (KIF5B protein, human) RN - 0 (RNA, Messenger) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret) RN - EC 3.6.4.4 (Kinesins) SB - IM MH - Aged MH - Aged, 80 and over MH - Asian People MH - Female MH - *Gene Expression MH - *Gene Rearrangement MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Japan MH - Kinesins/*genetics/metabolism MH - Lung Neoplasms/diagnosis/*genetics MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Proto-Oncogene Proteins c-ret/*genetics/metabolism MH - RNA, Messenger/genetics MH - Translocation, Genetic PMC - PMC3544433 OTO - NOTNLM OT - FISH OT - KIF5B/RET OT - RET expression OT - lung cancer EDAT- 2013/01/24 06:00 MHDA- 2013/01/24 06:01 PMCR- 2012/08/01 CRDT- 2013/01/24 06:00 PHST- 2012/03/21 00:00 [received] PHST- 2012/05/30 00:00 [revised] PHST- 2012/05/31 00:00 [accepted] PHST- 2013/01/24 06:00 [entrez] PHST- 2013/01/24 06:00 [pubmed] PHST- 2013/01/24 06:01 [medline] PHST- 2012/08/01 00:00 [pmc-release] AID - 10.1002/cam4.13 [doi] PST - ppublish SO - Cancer Med. 2012 Aug;1(1):68-75. doi: 10.1002/cam4.13. Epub 2012 Jul 12.