title: Pulmonary adenocarcinoma with enteric differentiation: Dissecting oncogenic genes alterations with DNA sequencing and FISH analysis.
abstract: Pulmonary Adenocarcinoma with Enteric Differentiation (PAED) is a rare subtype of adenocarcinoma of emerging interest, recently introduced in the 2015 WHO classification. However, little is known about major molecular signatures of this class of adenocarcinomas and information about new biomarkers totally lack.
  
  
  
  We examined the NRAS, PIK3CA, EGFR, KRAS and BRAF status through mass spectrometry sequencing and ALK rearrangement by FISH in a series of 8 PAEDs.
  
  
  
  1/8 (12.5%) case had a simultaneous PIK3CA mutation (E545K) and an EML4-ALK translocation. KRAS gene showed a mutation in the codon 12 in 4/8 of PAED (50%), NRAS, BRAF and EGFR genes were wild type in all tumor samples.
  
  
  
  We concluded that PIK3CA mutations and ALK rearrangement occur also in PAEDs, while NRAS mutations might be a very rare event similarly to pulmonary adenocarcinomas of conventional type. KRAS is the prevailing gene mutated in this class of adenocarcinoma.
authors.affiliation: Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, Italy. Electronic address: alessia.nottegar@univr.it.
authors.forename: Alessia
authors.initials: A
authors.lastname: Nottegar
authors.affiliation: Department of Molecular Biotechnology and Health Science, Center for Experimental Research and Medical Studies (CeRMS), University of Turin, 10126 Turin, Italy; Departments of Pathology and Pharmacology, Weill Cornell Cancer Center, Weill Cornell Medical College, Cornell University, 10065 New York, NY, USA.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tabbò
authors.affiliation: Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, Italy; Department of Pathology, Santa Chiara Hospital, 38122 Trento, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchini
authors.affiliation: Department of Thoracic Surgery, University of Turin, 10126 Turin, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Guerrera
authors.affiliation: Department of Molecular Biotechnology and Health Science and Center for Experimental Research and Medical Studies, University of Turin, 10126 Turin, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Gaudiano
authors.affiliation: Medical Oncology, University and Hospital Trust of Verona, 37134 Verona, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.affiliation: Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
authors.affiliation: Departments of Pathology and Pharmacology, Weill Cornell Cancer Center, Weill Cornell Medical College, Cornell University, 10065 New York, NY, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Inghirami
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D058534:Class I Phosphatidylinositol 3-Kinases; D003062:Codon; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D003062:Codon; C117307:KRAS protein, human; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: ALK; EGFR; Enteric; K-RAS; Lung adenocarcinoma; PIK3CA