title: Multidriver mutation analysis in pulmonary mucinous adenocarcinoma in Taiwan: identification of a rare CD74-NRG1 translocation case.
abstract: Several new chromosomal translocations resulting in driver fusion mutations have recently been discovered in non-small-cell lung cancer. The driver mutational patterns in pulmonary mucinous adenocarcinoma, a rare subtype of non-small-cell lung cancer, have not been well studied. A single-institute cohort study in Taiwan was performed to determine the mutations of epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), fusions of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and neuregulin 1 (NRG1) in patients diagnosed with pulmonary mucinous adenocarcinoma. We also examined NRG1 translocation in patients diagnosed as adenocarcinoma of other subtypes with wild-type EGFR, KRAS, ALK, and ROS1 genes. Surgical or biopsy specimens were collected from 13 patients with mucinous adenocarcinoma. Using the direct RNA sequencing method, we discovered a rare CD74-NRG1 fusion (8 %), an echinoderm microtubule-associated protein like 4 (EML4)-ALK fusion (17 %), and three KRAS mutations (25 %). No EGFR mutations or ROS1 rearrangements were detected. The rare CD74-NRG1 fusion positive patient presented with uncommon radiological features. We did not detect any CD74-NRG1 fusion in the 109 adenocarcinoma of other subtypes, which were all negative for EGFR, KRAS, ALK, and ROS1. The CD74-NRG1 fusion mutation is rare and may be exclusively present in patients with pulmonary mucinous adenocarcinoma. Patients harboring CD74-NRG1 positive tumors may present with uncommon imaging features.
authors.affiliation: Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, 220, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Gow
authors.forename: Shang-Gin
authors.initials: SG
authors.lastname: Wu
authors.forename: Yih-Leong
authors.initials: YL
authors.lastname: Chang
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Shih
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D059645:Mutation Rate; D020890:Neuregulin-1 / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D013624:Taiwan; D014178:Translocation, Genetic; D018631:ras Proteins / Q000235:genetics
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; C522504:EML4-ALK fusion protein, human; D000949:Histocompatibility Antigens Class II; C117307:KRAS protein, human; C094131:NRG1 protein, human; D020890:Neuregulin-1; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C045084:invariant chain; C000626173:ALK protein, human; C000626175:Alk protein, rat; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins