title: Whole exome sequencing of urachal adenocarcinoma reveals recurrent NF1 mutations.
abstract: 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.
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA, USA.|Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Harshabad
authors.initials: H
authors.lastname: Singh
authors.affiliation: Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.affiliation: Broad Institute, Cambridge, MA, USA.
authors.forename: Jaegil
authors.initials: J
authors.lastname: Kim
authors.affiliation: Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Van Hummelen
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Chin-Lee
authors.initials: CL
authors.lastname: Wu
authors.affiliation: Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Bass
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Saylor
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000369:Aged, 80 and over; D005260:Female; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D025542:Neurofibromin 1 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D000073359:Exome Sequencing; D055815:Young Adult
chemical_list: D025542:Neurofibromin 1
keywords: NF1; urachal adenocarcinoma; whole exome sequencing