Frequent somatic CDH1 loss-of-function mutations in plasmacytoid variant bladder cancer

Plasmacytoid bladder cancer is an aggressive histologic variant with a high risk of disease-specific mortality. Using whole-exome and targeted sequencing, we find that truncating somatic alterations in the CDH1 gene occur in 84% of plasmacytoid carcinomas and are specific to this histologic variant....

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Published inNature genetics Vol. 48; no. 4; pp. 356 - 358
Main Authors Al-Ahmadie, Hikmat A, Iyer, Gopa, Lee, Byron H, Scott, Sasinya N, Mehra, Rohit, Bagrodia, Aditya, Jordan, Emmet J, Gao, Sizhi Paul, Ramirez, Ricardo, Cha, Eugene K, Desai, Neil B, Zabor, Emily C, Ostrovnaya, Irina, Gopalan, Anuradha, Chen, Ying-Bei, Fine, Samson W, Tickoo, Satish K, Gandhi, Anupama, Hreiki, Joseph, Viale, Agnès, Arcila, Maria E, Dalbagni, Guido, Rosenberg, Jonathan E, Bochner, Bernard H, Bajorin, Dean F, Berger, Michael F, Reuter, Victor E, Taylor, Barry S, Solit, David B
Format Journal Article
LanguageEnglish
Published United States Nature Publishing Group 01.04.2016
Subjects
Antigens, CD
Bladder cancer
Cadherins - genetics
Cell Line, Tumor
Cell migration
Development and progression
DNA Mutational Analysis
DNA sequencing
Gene mutations
Genetic aspects
Genetic Association Studies
Genetic Predisposition to Disease
Health aspects
Histology
Humans
Identification and classification
Kinases
Medical prognosis
Medical research
Methods
Mortality
Multivariate Analysis
Mutation
Nucleotide sequencing
Plasmacytoma - genetics
Proportional Hazards Models
Studies
Tumors
Urinary Bladder Neoplasms - genetics
Urinary Bladder Neoplasms - mortality
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Summary:Plasmacytoid bladder cancer is an aggressive histologic variant with a high risk of disease-specific mortality. Using whole-exome and targeted sequencing, we find that truncating somatic alterations in the CDH1 gene occur in 84% of plasmacytoid carcinomas and are specific to this histologic variant. Consistent with the aggressive clinical behavior of plasmacytoid carcinomas, which frequently recur locally, CRISPR/Cas9-mediated knockout of CDH1 in bladder cancer cells enhanced cell migration.
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These authors contributed equally to this manuscript
ISSN:1061-4036
1546-1718
DOI:10.1038/ng.3503