Comprehensive somatic genome alterations of urachal carcinoma
- 27 March 2017
- journal article
- research article
- Published by BMJ in Journal of Medical Genetics
- Vol. 54 (8), 572-578
- https://doi.org/10.1136/jmedgenet-2016-104390
Abstract
Background Urachal cancer is a rare cancer that develops in the urachus. Because of its rarity, standard treatment therapies for urachal cancer are not established, and chemotherapeutic regimens for bladder cancer have been unsuccessful for patients with urachal cancer. Hence, we aim to understand a systematic molecular characterisation of urachal cancer. Methods We identified somatic single-nucleotide variations (SNVs)/indels and somatic copy number aberrations (SCNAs) in the 17 patients by using whole-exome sequencing (WES) and OncoScan platform (Affymetrix) as follows: tumour-normal paired sequencing (WES, n=10), tumour-only sequencing (WES, n=1; targeted deep sequencing, n=16), and OncoScan (n=17). Results Our analyses identified 27 genes with somatic SNVs and indels, as well as six genes (APC, COL5A1, KIF26B, LRP1B, SMAD4 and TP53) that were recurrent in at least two patients. By analysing the SCNAs, we found that the extent of chromosomal amplification was highly associated with the patient's cancer stage. Interestingly, 35% (6/17) of the patients had focal DNA amplifications in fibroblast growth factor receptor family genes. The integration of somatic SNVs, indels and SCNAs revealed significant alterations in the mitogen-activated protein kinase signalling pathways. Conclusions Our genome-wide analysis of urachal cancer suggests that molecular characteristics may be important for the treatment of urachal cancer.Keywords
Funding Information
- National Research Foundation of Korea
- Microsoft Research Asia
This publication has 34 references indexed in Scilit:
- Signatures of mutational processes in human cancerNature, 2013
- Expression Microarray Meta-Analysis Identifies Genes Associated with Ras/MAPK and Related Pathways in Progression of Muscle-Invasive Bladder Transition Cell CarcinomaPLOS ONE, 2013
- EXCAVATOR: detecting copy number variants from whole-exome sequencing dataGenome Biology, 2013
- Comprehensive molecular characterization of human colon and rectal cancerNature, 2012
- SIFT web server: predicting effects of amino acid substitutions on proteinsNucleic Acids Research, 2012
- Strelka: accurate somatic small-variant calling from sequenced tumor–normal sample pairsBioinformatics, 2012
- VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencingGenome Research, 2012
- Dindel: Accurate indel calls from short-read dataGenome Research, 2010
- Fast and accurate short read alignment with Burrows–Wheeler transformBioinformatics, 2009
- A census of human cancer genesNature Reviews Cancer, 2004