PMID- 23932363 OWN - NLM STAT- MEDLINE DCOM- 20140417 LR - 20211203 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 82 IP - 1 DP - 2013 Oct TI - Diagnostic method for the detection of KIF5B-RET transformation in lung adenocarcinoma. PG - 44-50 LID - S0169-5002(13)00318-8 [pii] LID - 10.1016/j.lungcan.2013.07.009 [doi] AB - KIF5B-RET fusions have recently been reported to occur in pulmonary adenocarcinomas, thereby being proposed as a novel genetic alteration in adenocarcinoma of the lung. However, clinically useful methods to detect RET-rearrangement in pulmonary adenocarcinoma have not been well established. 53 cases of lung adenocarcinomas harbored "triple (EGFR, KRAS and ALK)-negative" were tested for KIF5B-RET fusions using whole-transcriptome sequencing, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and long-range PCR. Dual color break-apart probes and KIF5B-RET fusion probes were used for FISH. Three different commercial antibodies against C-terminal RET protein were tested for IHC. Primers designed for 3 different variants of KIF5B-RET fusions were used for long-range PCR. Three patients (5.6%) showed RET rearrangement in whole-transcriptome sequencing, which were used as a gold standard. All those three patients were also positive in FISH for both KIF5B-RET fusion and RET break-apart probes. None of remaining patients showed positive result, resulting in 100% concordance rate of FISH and transcriptome sequencing methods. However, fused RET proteins were not detected by IHC in none of true positive patients. Moreover, 6 patients without RET fusions showed gain of gene copy number of both KIF5B and RET. All those three true positive cases were detected by long-range PCR methods and none with true negative cases were positive. Both FISH and PCR may be useful methods to detect novel KIF5B-RET rearrangements in pulmonary adenocarcinomas rather than IHC. However, as there may be additional variant of fusion mutation, FISH may be better than PCR method in terms of sensitivity. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Go, Heounjeong AU - Go H AD - Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Jung, Yoo Jin AU - Jung YJ FAU - Kang, Hyun Woong AU - Kang HW FAU - Park, In-Kyu AU - Park IK FAU - Kang, Chang-Hyun AU - Kang CH FAU - Lee, Jung Wan AU - Lee JW FAU - Ju, Young Seok AU - Ju YS FAU - Seo, Jeong-Sun AU - Seo JS FAU - Chung, Doo Hyun AU - Chung DH FAU - Kim, Young Tae AU - Kim YT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130809 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (KIF5B protein, human) RN - 0 (Oncogene Proteins, Fusion) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret) RN - EC 2.7.10.1 (RET protein, human) RN - EC 3.6.4.4 (Kinesins) SB - IM MH - Adenocarcinoma/*diagnosis/genetics MH - Adenocarcinoma of Lung MH - Aged MH - DNA Mutational Analysis MH - Female MH - Humans MH - Kinesins/*genetics MH - Lung Neoplasms/*diagnosis/genetics MH - Male MH - Middle Aged MH - Molecular Diagnostic Techniques MH - Oncogene Proteins, Fusion/*genetics MH - Polymerase Chain Reaction MH - Proto-Oncogene Proteins c-ret/*genetics MH - Sequence Analysis, DNA MH - Transcriptome OTO - NOTNLM OT - Biomarkers OT - Fluorescence in situ hybridization (FISH) OT - Immunohistochemistry (IHC) OT - Lung cancer OT - Polymerase chain reaction (PCR) EDAT- 2013/08/13 06:00 MHDA- 2014/04/18 06:00 CRDT- 2013/08/13 06:00 PHST- 2013/03/30 00:00 [received] PHST- 2013/06/29 00:00 [revised] PHST- 2013/07/11 00:00 [accepted] PHST- 2013/08/13 06:00 [entrez] PHST- 2013/08/13 06:00 [pubmed] PHST- 2014/04/18 06:00 [medline] AID - S0169-5002(13)00318-8 [pii] AID - 10.1016/j.lungcan.2013.07.009 [doi] PST - ppublish SO - Lung Cancer. 2013 Oct;82(1):44-50. doi: 10.1016/j.lungcan.2013.07.009. Epub 2013 Aug 9.