title: PTCH1 gene mutations in exon 17 and loss of heterozygosity on D9S180 microsatellite in sporadic and inherited human basal cell carcinomas.
abstract: BACKGROUND
  Basal cell carcinomas (BCCs) are the most frequent human cancer that results from malignant transformation of basal cells in the epidermis. Gorlin syndrome is a rare inherited autosomal dominant disease that predisposes with multiple BCCs and other birth defects. Both sporadic and inherited BCCs are associated with mutations in the tumor suppressor gene PTCH1, but there is still uncertainty on the role of its homolog PTCH2.
  
  
  OBJECTIVE
  To search for mutations and genomic instability in sporadic and inherited BCCs.
  
  
  METHODS
  DNA obtained from leukocytes and tumor cells was amplified by polymerase chain reaction regarding five exons of PTCH1 and PTCH2 and neighboring microsatellites. Exons were sequenced and compared with the GenBank database.
  
  
  RESULTS
  Only D9S180, of six microsatellites, showed loss of heterozygosity in three BCCs (two sporadic and one inherited). One sporadic BCC presented the mutation g.2885G>C in exon 17 of PTCH1, which predicts the substitution p.R962T in an external domain of the protein. In addition, the leukocytes and tumor cells of one patient with Gorlin syndrome showed the mutation g.2839T>G in the same exon and gene, which predicts a p.E947stop and truncated protein. All control and tumor samples presented IVS9 + 217T in intron 9 of PTCH1.
  
  
  CONCLUSIONS
  Mutations found in the PTCH1 gene and neighboring repetitive sequences may have contributed to the development of the studied BCCs.
authors.affiliation: Genetics Laboratory, Butantan Institute, Sao Paulo, Brazil.
authors.forename: Daniela C C
authors.initials: DC
authors.lastname: Santos
authors.forename: Peter G
authors.initials: PG
authors.lastname: Zaphiropoulos
authors.forename: Cyro F
authors.initials: CF
authors.lastname: Neto
authors.forename: Eugênio R A
authors.initials: ER
authors.lastname: Pimentel
authors.forename: José A
authors.initials: JA
authors.lastname: Sanches
authors.forename: Itamar R G
authors.initials: IR
authors.lastname: Ruiz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001478:Basal Cell Nevus Syndrome / Q000235:genetics*; D001483:Base Sequence; D002280:Basal Cell Carcinoma / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; D017354:Point Mutation; D011956:Receptors, Cell Surface / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: C000606236:PTCH1 protein, human; C000606238:PTCH2 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; D011956:Receptors, Cell Surface