Whole exome sequencing of urachal adenocarcinoma reveals recurrent NF1 mutations

Oncotarget. 2016 May 17;7(20):29211-5. doi: 10.18632/oncotarget.8640.


Urachal adenocarcinoma is a rare bladder malignancy arising from the urachal remnant. Given its rarity and the lack of knowledge about its genetic characteristics, optimal management of this cancer is not well defined. Practice patterns vary and outcomes remain poor. In order to identify the genomic underpinnings of this malignancy, we performed whole exome sequencing using seven tumor/normal pairs of formalin fixed archival specimens. We identified recurrent evidence of MAP-kinase pathway activation as three patients had neurofibromin 1 (NF1) mutations, with one of these patients also harboring an oncogenic KRAS G13D mutation. We also observed recurrent evidence of Wnt/β-catenin pathway activation as three patients had oncogenic mutations in APC or RNF43. In addition, somatic copy number analysis revealed focal chromosome 12p amplifications in three samples, resembling findings from testicular germ cell tumors. We describe the genomic landscape of this malignancy in our institutional cohort and propose investigation of the therapeutic potential for MAP-K pathway inhibition in the subset of patients who show evidence of its activation.

Keywords: NF1; urachal adenocarcinoma; whole exome sequencing.

MeSH terms

  • Adenocarcinoma / genetics*
  • Aged, 80 and over
  • Female
  • Genes, Neurofibromatosis 1
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neurofibromin 1 / genetics*
  • Urinary Bladder Neoplasms / genetics*
  • Whole Exome Sequencing
  • Young Adult


  • Neurofibromin 1

Supplementary concepts

  • Urachal adenocarcinoma