A High Frequency of Activating Extracellular Domain <i>ERBB2</i> (<i>HER2</i>) Mutation in Micropapillary Urothelial Carcinoma
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- Jeffrey S. Ross
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Kai Wang
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Laurie M. Gay
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Rami N. Al-Rohil
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Tipu Nazeer
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Christine E. Sheehan
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Timothy A. Jennings
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Geoff A. Otto
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Amy Donahue
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Jie He
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Gary Palmer
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Siraj Ali
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Michelle Nahas
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Geneva Young
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Elaine LaBrecque
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Garrett Frampton
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Rachel Erlich
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- John A. Curran
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Kristina Brennan
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Sean R. Downing
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Roman Yelensky
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Doron Lipson
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Matthew Hawryluk
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Vincent A. Miller
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
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- Philip J. Stephens
- Authors' Affiliations: 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York; and 2Foundation Medicine, Inc., Cambridge, Massachusetts
説明
<jats:title>Abstract</jats:title> <jats:p>Purpose: Micropapillary urothelial carcinoma (MPUC) is a rare and aggressive form of bladder cancer. We conducted genomic analyses [next-generation sequencing (NGS)] of MPUC and non-micropapillary urothelial bladder carcinomas (non-MPUC) to characterize the genomic landscape and identify targeted treatment options.</jats:p> <jats:p>Experimental Design: DNA was extracted from 40 μm of formalin-fixed paraffin-embedded sections from 15 MPUC and 64 non-MPUC tumors. Sequencing (NGS) was performed on hybridization-captured, adaptor ligation–based libraries to high coverage for 3,230 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. The results were evaluated for all classes of genomic alteration.</jats:p> <jats:p>Results: Mutations in the extracellular domain of ERBB2 were identified in 6 of 15 (40%) of MPUC: S310F (four cases), S310Y (one case), and R157W (one case). All six cases of MPUC with ERBB2 mutation were negative for ERBB2 amplification and Erbb2 overexpression. In contrast, 6 of 64 (9.4%) non-MPUC harbored an ERBB2 alteration, including base substitution (three cases), amplification (two cases), and gene fusion (one case), which is higher than the 2 of 159 (1.3%) protein-changing ERBB2 mutations reported for urinary tract cancer in COSMIC. The enrichment of ERBB2 alterations in MPUC compared with non-MPUC is significant both between this series (P < 0.0084) and for all types of urinary tract cancer in COSMIC (P < 0.001).</jats:p> <jats:p>Conclusions: NGS of MPUC revealed a high incidence of mutation in the extracellular domain of ERBB2, a gene for which there are five approved targeted therapies. NGS can identify genomic alteration, which inform treatment options for the majority of MPUC patients. Clin Cancer Res; 20(1); 68–75. ©2013 AACR.</jats:p>
収録刊行物
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- Clinical Cancer Research
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Clinical Cancer Research 20 (1), 68-75, 2014-01-01
American Association for Cancer Research (AACR)