000147359 001__ 147359 000147359 005__ 20240229120012.0 000147359 0247_ $$2doi$$a10.1016/j.lungcan.2019.10.005 000147359 0247_ $$2pmid$$apmid:31634654 000147359 0247_ $$2ISSN$$a0169-5002 000147359 0247_ $$2ISSN$$a1872-8332 000147359 0247_ $$2altmetric$$aaltmetric:69123292 000147359 037__ $$aDKFZ-2019-02480 000147359 041__ $$aeng 000147359 082__ $$a610 000147359 1001_ $$0P:(DE-HGF)0$$aJurmeister, Philipp$$b0 000147359 245__ $$aNext generation sequencing of lung adenocarcinoma subtypes with intestinal differentiation reveals distinct molecular signatures associated with histomorphology and therapeutic options. 000147359 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2019 000147359 3367_ $$2DRIVER$$aarticle 000147359 3367_ $$2DataCite$$aOutput Types/Journal article 000147359 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1581581451_5453 000147359 3367_ $$2BibTeX$$aARTICLE 000147359 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000147359 3367_ $$00$$2EndNote$$aJournal Article 000147359 500__ $$aEAL201LAL201 000147359 520__ $$aWe aim to provide a better understanding of the molecular landscape of primary lung adenocarcinomas with intestinal differentiation.Five invasive mucinous adenocarcinomas (IMA) and seven pulmonary enteric adenocarcinomas (PEAD) were included in this study. Furthermore, we analyzed six pulmonary colloid adenocarcinomas (CAD), including one primary tumor, one metastasis, and two sample pairs consisting of the primary colloid lung tumor and a matching metastasis and an acinar component, respectively. All samples were characterized using immunohistochemistry (TTF-1, CK7, CK20, CDX2, Ki-67, ALK and PD-L1) and a next generation sequencing panel covering 404 cancer-related genes (FoundationOne® gene panel).While Ki-67 expression was comparably low in IMA (range: 8-15%) and in primary CAD (range: 5-8%), we observed considerably higher proliferation rates in the non-colloid tumor compartment (16%) and metastases (72%) from CAD, as well as in the PEAD-group (36-71%). The overall tumor mutational burden was lowest in IMA (2.5 mutations per megabase), intermediate in CAD (5.8 mutations per megabase) and highest in PEAD (16.8 mutations per megabase). KRAS mutations were frequent in all three tumor subtypes, but TP53 mutations were mostly limited to PEAD. While chromosomal alterations were rare in IMA, we discovered MYC amplifications in three of four CAD. Comparing primary and metastatic CAD, we observed the acquisition of multiple mutations and chromosomal alterations. PEAD had a variety of chromosomal alterations, including two cases with RICTOR amplification. PD-L1 expression (20%, 50% and 80% of tumor cells) was limited to three PEAD samples, only. In conclusion, we provide a detailed insight into the molecular alterations across and within the different subtypes of pulmonary adenocarcinomas with intestinal differentiation. From a clinical perspective, we provide data on potential treatment strategies for patients with PEAD, including immunotherapy. 000147359 536__ $$0G:(DE-HGF)POF3-899$$a899 - ohne Topic (POF3-899)$$cPOF3-899$$fPOF III$$x0 000147359 588__ $$aDataset connected to CrossRef, PubMed, 000147359 7001_ $$0P:(DE-He78)ed973559beda9f54611a06471ba06776$$aVollbrecht, Claudia$$b1 000147359 7001_ $$aBehnke, Anke$$b2 000147359 7001_ $$aFrost, Nikolaj$$b3 000147359 7001_ $$aArnold, Alexander$$b4 000147359 7001_ $$aTreue, Denise$$b5 000147359 7001_ $$aRückert, Jens-Carsten$$b6 000147359 7001_ $$aNeudecker, Jens$$b7 000147359 7001_ $$0P:(DE-He78)db2e8cf0dd8fa826896839ffee4b1411$$aSchweizer, Leonille$$b8 000147359 7001_ $$aKlauschen, Frederick$$b9 000147359 7001_ $$aHorst, David$$b10 000147359 7001_ $$aHummel, Michael$$b11 000147359 7001_ $$aDietel, Manfred$$b12 000147359 7001_ $$0P:(DE-HGF)0$$avon Laffert, Maximilian$$b13 000147359 773__ $$0PERI:(DE-600)2025812-4$$a10.1016/j.lungcan.2019.10.005$$gVol. 138, p. 43 - 51$$p43 - 51$$tLung cancer$$v138$$x0169-5002$$y2019 000147359 909CO $$ooai:inrepo02.dkfz.de:147359$$pVDB 000147359 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ 000147359 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)db2e8cf0dd8fa826896839ffee4b1411$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ 000147359 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b13$$kDKFZ 000147359 9131_ $$0G:(DE-HGF)POF3-899$$1G:(DE-HGF)POF3-890$$2G:(DE-HGF)POF3-800$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vohne Topic$$x0 000147359 9141_ $$y2019 000147359 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz 000147359 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000147359 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000147359 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bLUNG CANCER : 2017 000147359 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000147359 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search 000147359 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC 000147359 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List 000147359 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000147359 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000147359 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000147359 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine 000147359 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5 000147359 9201_ $$0I:(DE-He78)L201-20160331$$kL201$$lDKTK Berlin$$x0 000147359 980__ $$ajournal 000147359 980__ $$aVDB 000147359 980__ $$aI:(DE-He78)L201-20160331 000147359 980__ $$aUNRESTRICTED