title: Multiple Hereditary Infundibulocystic Basal Cell Carcinoma Syndrome Associated With a Germline SUFU Mutation.
abstract: OBJECTIVE
  Multiple hereditary infundibulocystic basal cell carcinoma syndrome (MHIBCC) is a rare genodermatosis in which numerous indolent, well-differentiated basal cell carcinomas develop primarily on the face and genitals, without other features characteristic of basal cell nevus syndrome. The cause is unknown. The purpose of the study was to identify a genetic basis for the syndrome and a mechanism by which the associated tumors develop.
  
  
  METHODS
  Whole-exome sequencing of 5 tumors and a normal buccal mucosal sample from a patient with MHIBCC was performed. A conserved splice-site mutation in 1 copy of the suppressor of fused gene (SUFU) was identified in all tumor and normal tissue samples. Additional distinct deletions of the trans SUFU allele were identified in all tumor samples, none of which were present in the normal sample.
  
  
  CONCLUSIONS
  A germline SUFU mutation was present in a patient with MHIBCC, and additional acquired SUFU mutations underlie the development of infundibulocystic basal cell carcinomas. The downstream location of the SUFU gene within the sonic hedgehog pathway may explain why its loss is associated with relatively well-differentiated tumors and suggests that MHIBCC will not respond to therapeutic strategies, such as smoothened inhibitors, that target upstream components of this pathway.
authors.affiliation: Department of Dermatology, University of California, San Francisco2Department of Pathology, University of California, San Francisco.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Schulman
authors.affiliation: Department of Dermatology, University of California, San Francisco3Dermatology Research Unit, San Francisco Veterans Affairs Medical Center, San Francisco, California.
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Oh
authors.affiliation: NantOmics, LLC, Santa Cruz, California.
authors.forename: J Zachary
authors.initials: JZ
authors.lastname: Sanborn
authors.affiliation: Department of Dermatology, University of California, San Francisco2Department of Pathology, University of California, San Francisco.
authors.forename: Laura
authors.initials: L
authors.lastname: Pincus
authors.affiliation: Department of Dermatology, University of California, San Francisco2Department of Pathology, University of California, San Francisco.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: McCalmont
authors.affiliation: Department of Dermatology, University of California, San Francisco.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Cho
mesh_terms: D002280:Basal Cell Carcinoma / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics*; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D012097:Repressor Proteins / Q000235:genetics*; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013577:Syndrome
chemical_list: D012097:Repressor Proteins; C490764:SUFU protein, human