Whole exome sequencing of urachal adenocarcinoma reveals recurrent NF1 mutations: Beyond the Abstract

Urachal adenocarcinoma is a rare malignancy arising from the urachal embryologic remnant. The genomic landscape of these tumors is largely unexplored to date. A recent study by Singh et al. published in the journal Oncotarget examined the genetic changes in urachal carcinoma. The investigators performed whole exome sequencing of eight tumor/normal pairs of formalin fixed archival urachal carcinoma specimens.  

The study identified recurrent mutations in P53, NF1 and SMAD4 genes. The investigators also found focal recurrent amplifications of chromosome 12p although the functional significance of this finding is still unknown. The authors note that that the same chromosomal locus is recurrently amplified in testicular germ cell tumors, which is another embryonal tumor.

The investigators findings showing the presence of somatic NF1 mutations identified by this study in urachal carcinomas is very interesting and mirrors NF1 mutations in other malignancies like juvenile myelomonocytic leukemia, lung cancer and melanoma. Because NF1 mutations are involved in activating the RAS pathway, there has been interest in utilizing blockade of MEK and other members of the MAP-Kinase pathway. The results of this study suggest that a similar approach merits further study in urachal adenocarcinoma.

Written by: Bishoy Faltas, MD


Singh H, Liu Y, Xiao X, Lin L, Kim J, Van Hummelen P, Wu CL, Bass AJ, Saylor PJ. Whole exome sequencing of urachal adenocarcinoma reveals recurrent NF1 mutations. Oncotarget. 2016 Apr 7. doi: 10.18632/oncotarget.8640. [Epub ahead of print]