Somatic mutations in the PTCH, SMOH, SUFUH and TP53 genes in sporadic basal cell carcinomas

Br J Dermatol. 2005 Jan;152(1):43-51. doi: 10.1111/j.1365-2133.2005.06353.x.


Background: Basal cell carcinoma (BCC) of the skin is the most common human cancer. The genetic alterations underlying BCC development are only partly understood.

Objectives: To investigate further the molecular genetics of sporadic BCCs, we performed mutation analyses of 10 skin cancer-associated genes in 42 tumours.

Methods: Single-strand conformational polymorphism analysis followed by DNA sequencing was used to screen for mutations in the sonic hedgehog pathway genes PTCH, SMOH, SUFUH and GLI1, in the TP53 tumour suppressor gene, and in the proto-oncogenes NRAS, KRAS, HRAS, BRAF and CTNNB1. Microsatellite markers flanking the PTCH, SUFUH and TP53 loci at 9q22, 10q24 and 17p13, respectively, were studied for loss of heterozygosity (LOH).

Results: PTCH mutations were found in 28 of 42 tumours (67%). Microsatellite analysis revealed LOH on 9q22 in 20 of 38 tumours investigated (53%), including 14 tumours with and six tumours without PTCH mutations. SMOH mutations were identified in four of the 42 BCCs (10%) while two tumours demonstrated mutations in SUFUH, including one missense mutation and one silent mutation. None of the BCCs showed LOH at markers flanking the SUFUH locus. Seventeen BCCs (40%) carried TP53 mutations, with only three tumours showing evidence of biallelic TP53 inactivation. TP53 mutations were present in BCCs with and without mutations in PTCH, SMOH or SUFUH. Interestingly, 72% of the TP53 alterations were presumably ultraviolet (UV)-induced transition mutations. In contrast, only 40% of the PTCH and SMOH alterations corresponded to UV signature mutations. No mutations were identified in GLI1, NRAS, KRAS, HRAS, BRAF or CTNNB1.

Conclusions: Our data confirm the importance of PTCH, SMOH and TP53 mutations in the pathogenesis of sporadic BCCs. SUFUH alterations are restricted to individual cases while the other investigated genes do not appear to be important targets for mutations in BCCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Carcinoma, Basal Cell / genetics*
  • DNA Mutational Analysis / methods
  • DNA, Neoplasm / genetics
  • Female
  • Genes, p53
  • Humans
  • Loss of Heterozygosity
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Patched Receptors
  • Patched-1 Receptor
  • Polymorphism, Single-Stranded Conformational
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled / genetics
  • Repressor Proteins / genetics
  • Signal Transduction / genetics
  • Skin Neoplasms / genetics*
  • Smoothened Receptor


  • DNA, Neoplasm
  • Membrane Proteins
  • Neoplasm Proteins
  • PTCH1 protein, human
  • Patched Receptors
  • Patched-1 Receptor
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Repressor Proteins
  • SMO protein, human
  • SUFU protein, human
  • Smoothened Receptor