{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:24:04Z","timestamp":1790753044484,"version":"4.1.0"},"reference-count":27,"publisher":"BMJ","issue":"2","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2020,5,19]]},"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>The present study investigated the incidence and spectrum of human epidermal growth factor receptor 2 (HER2) mutations, associated clinicopathological characteristics and the co-occurrence of <jats:italic>HER2<\/jats:italic> gene amplification in the <jats:italic>HER2<\/jats:italic> gene mutated cases in non-small cell lung cancer (NSCLC).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>All patients with advanced lung adenocarcinoma (LUAD) who underwent broad genomic profiling by next generation sequencing (NGS) from 2015 to 2019 were included in the study. <jats:italic>HER2<\/jats:italic> gene amplification was checked in all the <jats:italic>HER2<\/jats:italic> gene mutated cases. Tumour tissues of all the mutated cases were examined by fluorescent in situ hybridisation (FISH).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Fifty-four (37.2%) out of the 145 cases harboured tier 1 driver mutations comprising <jats:italic>EGFR<\/jats:italic> in 22.1%, ALK rearrangements in 7.6% cases, <jats:italic>ROS1<\/jats:italic> rearrangements and <jats:italic>BRAF<\/jats:italic>\n                     <jats:sup>V600E<\/jats:sup> in 3.5% cases each, and <jats:italic>NTRK<\/jats:italic> fusion in 0.7% cases. Nine (6.2%) cases exhibited a significant genetic alteration in <jats:italic>HER2<\/jats:italic> gene (tiers 2 and 3) on NGS. The most common alteration was exon 20 insertion of amino acid sequence AYVM in five cases (p.E770_A771insAYVM) followed by insertion of YVMA (p.A771_Y772insYVMA) in one case, insGSP (p.V777_G778insGSP) in one case and two missense mutations: p.G776C and p.QA795C (novel variant). The median copy number of the HER2 gene was 3.21 while on FISH, the median HER2\/CEP17 ratio was 2.0.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>There is a relatively higher occurrence of <jats:italic>HER2<\/jats:italic> exon 20 mutations as primary oncogenic driver in NSCLC especially LUAD. Our cohort has demonstrated (p.E770_A771insAYVM) as the strikingly dominant insertion mutation against the most often globally reported (p.A771_Y772insYVMA).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jclinpath-2020-206730","type":"journal-article","created":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T17:19:51Z","timestamp":1591895991000},"page":"106-110","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Non-amplification genetic alterations of <i>HER2<\/i> gene in non-small cell lung carcinoma"],"prefix":"10.1136","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6517-3664","authenticated-orcid":false,"given":"Anurag","family":"Mehta","sequence":"first","affiliation":[{"name":"Deapartment of Laboratory Medicine, Transfusion Services and Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrinidhi","family":"Nathany","sequence":"additional","affiliation":[{"name":"Section of Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupal","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Department of Research, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev Kumar","family":"Sharma","sequence":"additional","affiliation":[{"name":"Section of Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mumtaz","family":"Saifi","sequence":"additional","affiliation":[{"name":"Section of Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ullas","family":"Batra","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,6,11]]},"reference":[{"key":"2025092503203988000_74.2.106.1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.5858\/2010-0454-RAR.1","article-title":"Her2: biology, detection, and clinical implications","volume":"135","author":"Gutierrez","year":"2011","journal-title":"Arch Pathol Lab Med"},{"key":"2025092503203988000_74.2.106.2","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.5858\/arpa.2018-0902-SA","article-title":"Human epidermal growth factor receptor 2 testing in breast cancer: American Society of clinical Oncology\/College of American pathologists clinical practice guideline focused update","volume":"142","author":"Wolff","year":"2018","journal-title":"Arch Pathol Lab Med"},{"key":"2025092503203988000_74.2.106.3","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.5858\/arpa.2016-0331-CP","article-title":"Her2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American pathologists, American Society for clinical pathology, and American Society of clinical oncology","volume":"140","author":"Bartley","year":"2016","journal-title":"Arch Pathol Lab Med"},{"key":"2025092503203988000_74.2.106.4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/esmoopen-2017-000279","article-title":"Activating HER2 mutations as emerging targets in multiple solid cancers","volume":"2","author":"Connell","year":"2017","journal-title":"ESMO Open"},{"key":"2025092503203988000_74.2.106.5","doi-asserted-by":"publisher","DOI":"10.1038\/nature13385"},{"key":"2025092503203988000_74.2.106.6","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1002\/cncr.30869","article-title":"Her2 mutations in lung adenocarcinomas: a report from the lung cancer mutation Consortium","volume":"123","author":"Pillai","year":"2017","journal-title":"Cancer"},{"key":"2025092503203988000_74.2.106.7","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e318234f0a2"},{"key":"2025092503203988000_74.2.106.8","unstructured":"Network NCC . 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