title: Urachal Carcinoma Shares Genomic Alterations with Colorectal Carcinoma and May Respond to Epidermal Growth Factor Inhibition.
abstract: Metastatic urachal carcinoma is a rare, understudied, and aggressive malignancy with limited treatment options. Histologically, urachal carcinomas resemble enteric adenocarcinomas and anecdotally respond to systemic therapies utilized in colorectal cancer. Targeted exome sequencing of archival primary tumor tissue from a patient with metastatic urachal cancer revealed EGFR amplification and wild-type KRAS. The patient was treated with cetuximab, a monoclonal antibody directed against EGFR, as a single agent, and achieved a response lasting more than 8 mo. Subsequent whole-exome sequencing revealed no additional alterations likely to be associated with cetuximab sensitivity. Formalin-fixed, paraffin-embedded tumor specimens from nine additional urachal cancers were subjected to targeted exome sequencing. Mitogen-activated protein kinase (MAPK) pathway mutations were found in four of the nine samples, but no EGFR amplification was detected. Importantly, APC mutations were detected in two of the nine patients. To our knowledge, this is the first report of a response to single-agent cetuximab in a patient with metastatic urachal cancer and of molecular analysis to probe the basis for sensitivity. On the basis of these findings and the histologic, and now genomic, similarities with colorectal cancer, monoclonal antibodies directed at EGFR could be used in the treatment of metastatic urachal cancer.
  
  
  
  Urachal cancers are morphologically and genomically similar to colon adenocarcinomas and may respond to drugs targeting the epidermal growth factor receptor.
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Spanish Society of Medical Oncology, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Collazo-Lorduy
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Mireia
authors.initials: M
authors.lastname: Castillo-Martin
authors.affiliation: Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Patel
authors.affiliation: Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Gopa
authors.initials: G
authors.lastname: Iyer
authors.affiliation: Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Emmet
authors.initials: E
authors.lastname: Jordan
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Hikmat
authors.initials: H
authors.lastname: Al-Ahmadie
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Issa
authors.initials: I
authors.lastname: Leonard
authors.affiliation: Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
authors.affiliation: Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Russell B
authors.initials: RB
authors.lastname: McBride
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
authors.affiliation: Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Solit
authors.affiliation: Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Sfakianos
authors.affiliation: Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: matthew.galsky@mssm.edu.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Galsky
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068818:Cetuximab / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D000071185:Pharmacogenomic Testing; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000073359:Exome Sequencing
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab
keywords: Epidermal growth-factor; Genomic alterations; Inhibition; Urachal carcinoma