{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:10:10Z","timestamp":1783444210837,"version":"3.54.6"},"reference-count":24,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Some pancreatic ductal-type (PDADK) and lung adenocarcinomas (LADK) lacking other molecular drivers are reported to harbor NRG1 fusions as potential novel therapeutic targets. We investigated the feasibility of a fluorescent in situ hybridization (FISH)-based diagnosis of NRG1 fusions in a case series of PDADK and LADK lacking other identified oncogenic drivers. First, among a case series of PDADK, KRAS analyses (PCR followed in PCR-negative cases by RNA sequencing\u2014RNAseq) found 27\/162 (16.7%) KRAS wild-type cases, among which 1\/162 (0.6%) NRG1 fusion was diagnosed using FISH. Secondly, among a case series of LDAK, 191\/446 (42.8%) cases had no molecular alterations in EGFR, KRAS, BRAF, HER2, MET, ALK, ROS1 and RET according to NGS and FISH analyses and, among them, 4\/446 (0.9%) cases had NRG1 fusions using FISH. Finally, four additional cases out of the two previously mentioned cases series (1 PDADK and 3 LADK) with NRG1 fusions diagnosed by first-line RNAseq were also concluded as NRG1 FISH-positive. The NRG1 FISH tests for the nine NRG1 FISH-positive cases resulted in 50% to 80% of positive tumor nuclei, all with single 3\u2032-NRG1 FISH signals. In our series, of the 22 cases analyzed with both NRG1 FISH (positivity criterion of at least 15% of tumor nuclei with a split between the 5\u2032- and the 3\u2032- parts of the probes and\/or isolated single 3\u2032-NRG1 signal) and RNAseq, 17 cases were FISH\u2013 RNAseq\u2013 and 5 cases were FISH+ RNAseq+ (no FISH+ RNAseq\u2013 or FISH\u2013 RNAseq+ cases in our study) resulting in 100% sensibility and specificity for the NRG1 FISH test. In the case of no access to RNAseq, NRG1 FISH consists of a valuable tool searching for NRG1 fusions in patients with advanced cancers.<\/jats:p>","DOI":"10.3390\/cancers17142347","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T11:52:58Z","timestamp":1752580378000},"page":"2347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fluorescent In Situ Hybridization Testing Allows the Diagnosis of NRG1 Gene Fusions in Lung and Pancreas Cancers with No Other Identified Oncogenic Driver"],"prefix":"10.3390","volume":"17","author":[{"given":"Clara","family":"Bastard","sequence":"first","affiliation":[{"name":"CHU Brest, Service d\u2019Anatomie et Cytologie Pathologiques, F-29200 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0352-5406","authenticated-orcid":false,"given":"Charline","family":"Caumont","sequence":"additional","affiliation":[{"name":"CHU Bordeaux, Department of Tumor Biology, F-33600 Pessac, France"},{"name":"BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, Univ. Bordeaux, F-33000 Bordeaux, France"},{"name":"Tumor Bank and Tumor Biology Laboratory, Bordeaux University Hospital, F-33600 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Samaison","sequence":"additional","affiliation":[{"name":"Ouest Pathologie, F-29000 Quimper, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Quintin-Rou\u00e9","sequence":"additional","affiliation":[{"name":"CHU Brest, Service d\u2019Anatomie et Cytologie Pathologiques, F-29200 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Doucet","sequence":"additional","affiliation":[{"name":"CHU Brest, Service d\u2019Anatomie et Cytologie Pathologiques, F-29200 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Marcorelles","sequence":"additional","affiliation":[{"name":"CHU Brest, Service d\u2019Anatomie et Cytologie Pathologiques, F-29200 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Le Mar\u00e9chal","sequence":"additional","affiliation":[{"name":"CHU Brest, Service de G\u00e9n\u00e9tique Mol\u00e9culaire, F-29200 Brest, France"},{"name":"Univ Brest, Inserm, CHU de Brest, UMR1078, F-29200 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0305-0850","authenticated-orcid":false,"given":"Jean-Philippe","family":"Merlio","sequence":"additional","affiliation":[{"name":"CHU Bordeaux, Department of Tumor Biology, F-33600 Pessac, France"},{"name":"BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, Univ. Bordeaux, F-33000 Bordeaux, France"},{"name":"Tumor Bank and Tumor Biology Laboratory, Bordeaux University Hospital, F-33600 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Cappellen","sequence":"additional","affiliation":[{"name":"CHU Bordeaux, Department of Tumor Biology, F-33600 Pessac, France"},{"name":"BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, Univ. Bordeaux, F-33000 Bordeaux, France"},{"name":"Tumor Bank and Tumor Biology Laboratory, Bordeaux University Hospital, F-33600 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0230-2905","authenticated-orcid":false,"given":"Arnaud","family":"Uguen","sequence":"additional","affiliation":[{"name":"CHU Brest, Service d\u2019Anatomie et Cytologie Pathologiques, F-29200 Brest, France"},{"name":"Univ Brest, Inserm, CHU de Brest, LBAI, UMR1227, F-29200 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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