title: Differential mutation frequencies in metastatic cutaneous squamous cell carcinomas versus primary tumors.
abstract: Exome and targeted sequencing studies have identified potential driver mutations for a variety of tumor types. Cutaneous squamous cell carcinoma (cSCC) is one of the most highly mutated cancers but typically is associated with low rates of metastasis and high survival rates. Nevertheless, metastatic cSCC is a significant health threat; up to 8800 individuals die each year of this disease.
  
  
  
  Because it is difficult to predict which cSCCs are more likely to metastasize, and because to the best of the authors' knowledge there are no targeted therapies specifically designated for patients with metastatic cSCC, exome and/or targeted sequencing of 18 metastatic and 10 primary cSCCs was performed to identify mutations that were more frequent in metastatic tumors and might be targeted for therapeutic benefit. The authors compared their results with published sequencing results of an additional 223 primary tumors and 68 metastatic cSCCs.
  
  
  
  The authors identified genes demonstrating higher mutation frequencies in metastatic cSCC compared with primary tumors, including the chromatin remodeling gene lysine methyltransferase 2D (KMT2D) and the classic skin tumor suppressor tumor protein p53 (TP53), which was found to be mutated in 54% of primary tumors compared with 85% of metastatic tumors (P<.0001).
  
  
  
  These studies appear to uncover potential pathways that are important in metastatic cSCC and that broaden understanding of the biology contributing to aggressive tumor behavior. These results may lead to new therapeutic strategies. Cancer 2017;123:1184-1193. © 2016 American Cancer Society.
authors.affiliation: Department of Biomedical Informatics, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: Ayse Selen
authors.initials: AS
authors.lastname: Yilmaz
authors.affiliation: Department of Biomedical Informatics, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: Hatice Gulcin
authors.initials: HG
authors.lastname: Ozer
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Gillespie
authors.affiliation: Department of Internal Medicine, Division of Human Genetics, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.|Department of Pathology, Division of Dermatopathology, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Allain
authors.affiliation: Department of Internal Medicine, Division of Human Genetics, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: Madison N
authors.initials: MN
authors.lastname: Bernhardt
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: Karina Colossi
authors.initials: KC
authors.lastname: Furlan
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: Leticia T F
authors.initials: LT
authors.lastname: Castro
authors.affiliation: Department of Pathology, Division of Dermatopathology, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: Sara B
authors.initials: SB
authors.lastname: Peters
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Priyadharsini
authors.initials: P
authors.lastname: Nagarajan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Kang
authors.affiliation: Department of Pathology and Laboratory Medicine, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.|Comprehensive Cancer Center, and Arthur G. James Cancer Hospital and Richard J. Solove Research Institute,The Ohio State University, Columbus, Ohio.
authors.forename: O Hans
authors.initials: OH
authors.lastname: Iwenofu
authors.affiliation: Comprehensive Cancer Center, and Arthur G. James Cancer Hospital and Richard J. Solove Research Institute,The Ohio State University, Columbus, Ohio.|Division of Medical Oncology, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.
authors.forename: Thomas
authors.initials: T
authors.lastname: Olencki
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.|Comprehensive Cancer Center, and Arthur G. James Cancer Hospital and Richard J. Solove Research Institute,The Ohio State University, Columbus, Ohio.
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Teknos
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.|Department of Internal Medicine, Division of Human Genetics, The Ohio State Wexner Medical Center, The Ohio State University, Columbus, Ohio.|Comprehensive Cancer Center, and Arthur G. James Cancer Hospital and Richard J. Solove Research Institute,The Ohio State University, Columbus, Ohio.
authors.forename: Amanda Ewart
authors.initials: AE
authors.lastname: Toland
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: KMT2D; TP53; cutaneous squamous cell carcinoma; exome sequencing; metastasis; mutation frequencies