{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T13:54:19Z","timestamp":1772805259708,"version":"3.50.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T00:00:00Z","timestamp":1534377600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/DTP-PIC\/2500\/2014"],"award-info":[{"award-number":["PTDC\/DTP-PIC\/2500\/2014"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Norte Portugal Regional Programme","award":["NORTE-01-0145-FEDER-000029"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000029"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1186\/s12885-018-4736-4","type":"journal-article","created":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T08:57:14Z","timestamp":1534409834000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Simultaneous detection of lung fusions using a multiplex RT-PCR next generation sequencing-based approach: a multi-institutional research study"],"prefix":"10.1186","volume":"18","author":[{"given":"Cecily P.","family":"Vaughn","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7132-4094","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Costa","sequence":"additional","affiliation":[]},{"given":"Harriet E.","family":"Feilotter","sequence":"additional","affiliation":[]},{"given":"Rosella","family":"Petraroli","sequence":"additional","affiliation":[]},{"given":"Varun","family":"Bagai","sequence":"additional","affiliation":[]},{"given":"Anna Maria","family":"Rachiglio","sequence":"additional","affiliation":[]},{"given":"Federica Zito","family":"Marino","sequence":"additional","affiliation":[]},{"given":"Bastiaan","family":"Tops","sequence":"additional","affiliation":[]},{"given":"Henriette M.","family":"Kurth","sequence":"additional","affiliation":[]},{"given":"Kazuko","family":"Sakai","sequence":"additional","affiliation":[]},{"given":"Andrea","family":"Mafficini","sequence":"additional","affiliation":[]},{"given":"Roy R. L.","family":"Bastien","sequence":"additional","affiliation":[]},{"given":"Anne","family":"Reiman","sequence":"additional","affiliation":[]},{"given":"Delphine","family":"Le Corre","sequence":"additional","affiliation":[]},{"given":"Alexander","family":"Boag","sequence":"additional","affiliation":[]},{"given":"Susan","family":"Crocker","sequence":"additional","affiliation":[]},{"given":"Michel","family":"Bihl","sequence":"additional","affiliation":[]},{"given":"Astrid","family":"Hirschmann","sequence":"additional","affiliation":[]},{"given":"Aldo","family":"Scarpa","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 Carlos","family":"Machado","sequence":"additional","affiliation":[]},{"given":"H\u00e9l\u00e8ne","family":"Blons","sequence":"additional","affiliation":[]},{"given":"Orla","family":"Sheils","sequence":"additional","affiliation":[]},{"given":"Kelli","family":"Bramlett","sequence":"additional","affiliation":[]},{"given":"Marjolijn J. L.","family":"Ligtenberg","sequence":"additional","affiliation":[]},{"given":"Ian A.","family":"Cree","sequence":"additional","affiliation":[]},{"given":"Nicola","family":"Normanno","sequence":"additional","affiliation":[]},{"given":"Kazuto","family":"Nishio","sequence":"additional","affiliation":[]},{"given":"Pierre","family":"Laurent-Puig","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2018,8,16]]},"reference":[{"issue":"7511","key":"4736_CR1","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/nature13385","volume":"511","author":"Cancer Genome Atlas Research N","year":"2014","unstructured":"Cancer Genome Atlas Research N. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511(7511):543\u201350.","journal-title":"Nature"},{"issue":"7216","key":"4736_CR2","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/nature07423","volume":"455","author":"L Ding","year":"2008","unstructured":"Ding L, Getz G, Wheeler DA, Mardis ER, McLellan MD, Cibulskis K, Sougnez C, Greulich H, Muzny DM, Morgan MB, et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature. 2008;455(7216):1069\u201375.","journal-title":"Nature"},{"issue":"5","key":"4736_CR3","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1097\/JTO.0000000000000516","volume":"10","author":"LM Sholl","year":"2015","unstructured":"Sholl LM, Aisner DL, Varella-Garcia M, Berry LD, Dias-Santagata D, Wistuba II, Chen H, Fujimoto J, Kugler K, Franklin WA, et al. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: the lung Cancer mutation consortium experience. J Thorac Oncol. 2015;10(5):768\u201377.","journal-title":"J Thorac Oncol"},{"issue":"7153","key":"4736_CR4","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/nature05945","volume":"448","author":"M Soda","year":"2007","unstructured":"Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448(7153):561\u20136.","journal-title":"Nature"},{"issue":"6","key":"4736_CR5","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1016\/j.cell.2007.11.025","volume":"131","author":"K Rikova","year":"2007","unstructured":"Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007;131(6):1190\u2013203.","journal-title":"Cell"},{"issue":"3","key":"4736_CR6","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/nm.2644","volume":"18","author":"T Kohno","year":"2012","unstructured":"Kohno T, Ichikawa H, Totoki Y, Yasuda K, Hiramoto M, Nammo T, Sakamoto H, Tsuta K, Furuta K, Shimada Y, et al. KIF5B-RET fusions in lung adenocarcinoma. Nat Med. 2012;18(3):375\u20137.","journal-title":"Nat Med"},{"issue":"3","key":"4736_CR7","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/nm.2658","volume":"18","author":"K Takeuchi","year":"2012","unstructured":"Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H, et al. RET, ROS1 and ALK fusions in lung cancer. Nat Med. 2012;18(3):378\u201381.","journal-title":"Nat Med"},{"issue":"5","key":"4736_CR8","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1038\/cr.2012.27","volume":"22","author":"F Li","year":"2012","unstructured":"Li F, Feng Y, Fang R, Fang Z, Xia J, Han X, Liu XY, Chen H, Liu H, Ji H. Identification of RET gene fusion by exon array analyses in \u201cpan-negative\u201d lung cancer from never smokers. Cell Res. 2012;22(5):928\u201331.","journal-title":"Cell Res"},{"issue":"11","key":"4736_CR9","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1038\/nm.3352","volume":"19","author":"A Vaishnavi","year":"2013","unstructured":"Vaishnavi A, Capelletti M, Le AT, Kako S, Butaney M, Ercan D, Mahale S, Davies KD, Aisner DL, Pilling AB, et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med. 2013;19(11):1469\u201372.","journal-title":"Nat Med"},{"issue":"16","key":"4736_CR10","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.2217\/fon-2016-0050","volume":"12","author":"A Uguen","year":"2016","unstructured":"Uguen A, De Braekeleer M. ROS1 fusions in cancer: a review. Future Oncol. 2016;12(16):1911\u201328.","journal-title":"Future Oncol"},{"issue":"13","key":"4736_CR11","doi-asserted-by":"publisher","first-page":"4275","DOI":"10.1158\/1078-0432.CCR-08-0168","volume":"14","author":"JP Koivunen","year":"2008","unstructured":"Koivunen JP, Mermel C, Zejnullahu K, Murphy C, Lifshits E, Holmes AJ, Choi HG, Kim J, Chiang D, Thomas R, et al. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res. 2008;14(13):4275\u201383.","journal-title":"Clin Cancer Res"},{"key":"4736_CR12","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.lungcan.2016.04.022","volume":"97","author":"S Scarpino","year":"2016","unstructured":"Scarpino S, Rampioni Vinciguerra GL, Di Napoli A, Fochetti F, Uccini S, Iacono D, Marchetti P, Ruco L. High prevalence of ALK+\/ROS1+ cases in pulmonary adenocarcinoma of adoloscents and young adults. Lung Cancer. 2016;97:95\u20138.","journal-title":"Lung Cancer"},{"issue":"2","key":"4736_CR13","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.lungcan.2014.02.007","volume":"84","author":"Y Pan","year":"2014","unstructured":"Pan Y, Zhang Y, Li Y, Hu H, Wang L, Li H, Wang R, Ye T, Luo X, Zhang Y, et al. ALK, ROS1 and RET fusions in 1139 lung adenocarcinomas: a comprehensive study of common and fusion pattern-specific clinicopathologic, histologic and cytologic features. Lung Cancer. 2014;84(2):121\u20136.","journal-title":"Lung Cancer"},{"issue":"7","key":"4736_CR14","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1634\/theoncologist.2013-0095","volume":"18","author":"JF Gainor","year":"2013","unstructured":"Gainor JF, Shaw AT. Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist. 2013;18(7):865\u201375.","journal-title":"Oncologist"},{"key":"4736_CR15","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1002\/jcb.240630505","volume":"24","author":"RM Phelps","year":"1996","unstructured":"Phelps RM, Johnson BE, Ihde DC, Gazdar AF, Carbone DP, McClintock PR, Linnoila RI, Matthews MJ, Bunn PA Jr, Carney D, et al. NCI-navy medical oncology branch cell line data base. J Cell Biochem Suppl. 1996;24:32\u201391.","journal-title":"J Cell Biochem Suppl"},{"issue":"4","key":"4736_CR16","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1002\/(SICI)1098-2264(199804)21:4<308::AID-GCC4>3.0.CO;2-2","volume":"21","author":"AK Virmani","year":"1998","unstructured":"Virmani AK, Fong KM, Kodagoda D, McIntire D, Hung J, Tonk V, Minna JD, Gazdar AF. Allelotyping demonstrates common and distinct patterns of chromosomal loss in human lung cancer types. Genes chromosomes cancer. 1998;21(4):308\u201319.","journal-title":"Genes chromosomes cancer"},{"issue":"12","key":"4736_CR17","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1097\/JTO.0b013e3182721ed1","volume":"7","author":"D Matsubara","year":"2012","unstructured":"Matsubara D, Kanai Y, Ishikawa S, Ohara S, Yoshimoto T, Sakatani T, Oguni S, Tamura T, Kataoka H, Endo S, et al. Identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line, LC-2\/ad. J Thorac Oncol. 2012;7(12):1872\u20136.","journal-title":"J Thorac Oncol"},{"issue":"17","key":"4736_CR18","doi-asserted-by":"publisher","first-page":"4570","DOI":"10.1158\/1078-0432.CCR-12-0550","volume":"18","author":"KD Davies","year":"2012","unstructured":"Davies KD, Le AT, Theodoro MF, Skokan MC, Aisner DL, Berge EM, Terracciano LM, Cappuzzo F, Incarbone M, Roncalli M, et al. Identifying and targeting ROS1 gene fusions in non-small cell lung cancer. Clin Cancer Res. 2012;18(17):4570\u20139.","journal-title":"Clin Cancer Res"},{"issue":"8","key":"4736_CR19","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1016\/j.molonc.2014.06.001","volume":"8","author":"E Ardini","year":"2014","unstructured":"Ardini E, Bosotti R, Borgia AL, De Ponti C, Somaschini A, Cammarota R, Amboldi N, Raddrizzani L, Milani A, Magnaghi P, et al. The TPM3-NTRK1 rearrangement is a recurring event in colorectal carcinoma and is associated with tumor sensitivity to TRKA kinase inhibition. Mol Oncol. 2014;8(8):1495\u2013507.","journal-title":"Mol Oncol"},{"issue":"11","key":"4736_CR20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112159","volume":"9","author":"L Tembuyser","year":"2014","unstructured":"Tembuyser L, Tack V, Zwaenepoel K, Pauwels P, Miller K, Bubendorf L, Kerr K, Schuuring E, Thunnissen E, Dequeker EM. The relevance of external quality assessment for molecular testing for ALK positive non-small cell lung cancer: results from two pilot rounds show room for optimization. PLoS One. 2014;9(11):e112159.","journal-title":"PLoS One"},{"issue":"7","key":"4736_CR21","doi-asserted-by":"publisher","first-page":"796","DOI":"10.5858\/arpa.2011-0321-OA","volume":"136","author":"ML Wallander","year":"2012","unstructured":"Wallander ML, Geiersbach KB, Tripp SR, Layfield LJ. Comparison of reverse transcription-polymerase chain reaction, immunohistochemistry, and fluorescence in situ hybridization methodologies for detection of echinoderm microtubule-associated proteinlike 4-anaplastic lymphoma kinase fusion-positive non-small cell lung carcinoma: implications for optimal clinical testing. Arch Pathol Lab Med. 2012;136(7):796\u2013803.","journal-title":"Arch Pathol Lab Med"},{"issue":"2","key":"4736_CR22","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.jmoldx.2013.11.007","volume":"16","author":"ME Lira","year":"2014","unstructured":"Lira ME, Choi YL, Lim SM, Deng S, Huang D, Ozeck M, Han J, Jeong JY, Shim HS, Cho BC, et al. A single-tube multiplexed assay for detecting ALK, ROS1, and RET fusions in lung cancer. J Mol Diagn. 2014;16(2):229\u201343.","journal-title":"J Mol Diagn"},{"issue":"7","key":"4736_CR23","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1097\/JTO.0b013e3182904e22","volume":"8","author":"KF To","year":"2013","unstructured":"To KF, Tong JH, Yeung KS, Lung RW, Law PP, Chau SL, Kang W, Tong CY, Chow C, Chan AW, et al. Detection of ALK rearrangement by immunohistochemistry in lung adenocarcinoma and the identification of a novel EML4-ALK variant. J Thorac Oncol. 2013;8(7):883\u201391.","journal-title":"J Thorac Oncol"},{"issue":"11","key":"4736_CR24","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1097\/JTO.0000000000000665","volume":"10","author":"X Gao","year":"2015","unstructured":"Gao X, Sholl LM, Nishino M, Heng JC, Janne PA, Oxnard GR. Clinical implications of variant ALK FISH rearrangement patterns. J Thorac Oncol. 2015;10(11):1648\u201352.","journal-title":"J Thorac Oncol"},{"issue":"6","key":"4736_CR25","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1634\/theoncologist.2015-0497","volume":"21","author":"SM Ali","year":"2016","unstructured":"Ali SM, Hensing T, Schrock AB, Allen J, Sanford E, Gowen K, Kulkarni A, He J, Suh JH, Lipson D, et al. Comprehensive genomic profiling identifies a subset of Crizotinib-responsive ALK-rearranged non-small cell lung Cancer not detected by fluorescence in situ hybridization. Oncologist. 2016;21(6):762\u201370.","journal-title":"Oncologist"},{"issue":"1","key":"4736_CR26","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/1755-8166-5-44","volume":"5","author":"Z Dai","year":"2012","unstructured":"Dai Z, Kelly JC, Meloni-Ehrig A, Slovak ML, Boles D, Christacos NC, Bryke CR, Schonberg SA, Otani-Rosa J, Pan Q, et al. Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas. Mol Cytogenet. 2012;5(1):44.","journal-title":"Mol Cytogenet"},{"issue":"1","key":"4736_CR27","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1002\/gcc.22297","volume":"55","author":"N Pfarr","year":"2016","unstructured":"Pfarr N, Stenzinger A, Penzel R, Warth A, Dienemann H, Schirmacher P, Weichert W, Endris V. High-throughput diagnostic profiling of clinically actionable gene fusions in lung cancer. Genes chromosomes cancer. 2016;55(1):30\u201344.","journal-title":"Genes chromosomes cancer"},{"issue":"10","key":"4736_CR28","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1097\/JTO.0000000000000280","volume":"9","author":"A Marchetti","year":"2014","unstructured":"Marchetti A, Barberis M, Papotti M, Rossi G, Franco R, Malatesta S, Buttitta F, Ardizzoni A, Crino L, Gridelli C, et al. ALK rearrangement testing by FISH analysis in non-small-cell lung cancer patients: results of the first italian external quality assurance scheme. J Thorac Oncol. 2014;9(10):1470\u20136.","journal-title":"J Thorac Oncol"}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-018-4736-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12885-018-4736-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-018-4736-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,22]],"date-time":"2019-09-22T05:44:53Z","timestamp":1569131093000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/s12885-018-4736-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,16]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["4736"],"URL":"https:\/\/doi.org\/10.1186\/s12885-018-4736-4","relation":{},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,16]]},"assertion":[{"value":"9 November 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 August 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 August 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Samples were retrieved from the archives of the collaborating institutions and de-identified. For the following institutions, the study was interpreted as a service improvement not requiring specific research ethics committee approval as stated in the EU Clinical Trials Directive (2001\/20\/EC): Radboud university medical center, VIOLLIER (assay performed by Viollier, samples mainly from University Hospital Basel and Luzerner Kantonsspital, Switzerland), Applied Research on Cancer Centre (ARC-NET), University Hospitals Coventry and Warwickshire (UHCW), Institut National de la Sante et de la Recherche Medicale (INSERM), and Centro di Ricerche Oncologiche di Mercogliano (CROM). Samples from the following institutions were used under approved Institutional Review Board protocols: ARUP Laboratories (ARUP Laboratories Ethics Committee approval 24,487), Queen\u2019s University (Health Sciences and Affiliated Teaching Hospitals Research Ethics Board approval 6,010,968), and Kinki University (Institutional Review Board of Kindai University Faculty of Medicine approval 22\u2013106). Samples from Ipatimup were used in accordance with Article 19 (\u201cDNA Banks and Other Biological Products\u201d) of Portuguese Law No. 12\/2005 of 26 January (\u201cPersonal genetic information and health information\u201d).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Thermo Fisher Scientific provided reagents for this study to participating laboratories at a discount. Travel funds were partially reimbursed for consortium members to attend a group meeting. Authors R.P., V.B., and K.B. are employed by Thermo Fisher Scientific. NN is a member of the editorial board (Associate Editor) of this journal.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"828"}}