Multidriver mutation analysis in pulmonary mucinous adenocarcinoma in Taiwan: identification of a rare CD74-NRG1 translocation case

Med Oncol. 2014 Jul;31(7):34. doi: 10.1007/s12032-014-0034-4. Epub 2014 Jun 10.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Mucinous / genetics*
  • Adenocarcinoma, Mucinous / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase
  • Antigens, Differentiation, B-Lymphocyte / genetics*
  • Asian Continental Ancestry Group / genetics
  • Base Sequence
  • ErbB Receptors / genetics
  • Female
  • Histocompatibility Antigens Class II / genetics*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation Rate
  • Mutation*
  • Neuregulin-1 / genetics*
  • Oncogene Proteins, Fusion / genetics
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Receptor Protein-Tyrosine Kinases / genetics
  • Taiwan
  • Translocation, Genetic
  • ras Proteins / genetics

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • EML4-ALK fusion protein, human
  • Histocompatibility Antigens Class II
  • KRAS protein, human
  • NRG1 protein, human
  • Neuregulin-1
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • invariant chain
  • ALK protein, human
  • Alk protein, rat
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • ROS1 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins