jeudi 17 mai 2012

Mutated genes in cancer (69) – PTCH1


In databases:

● Entrez ( 5727 or PTCH1
● Ensembl ( ENSG00000185920
● UniProt ( Q13635
● GeneCards ( PTCH1
● HGNC ( 9585 or PTCH1

Gene locus:


Protein name:

Patched 1

Protein Size:

1447 amino acids; about 161 kDa


The protein encoded by PTCH1 acts as a receptor for sonic hedgehog, a secreted molecule implicated in the formation of embryonic structures and in tumorigenesis, as well as indian hedgehog and desert hedgehog. Associates with the smoothened protein (SMO) to transduce the hedgehog's proteins signal. PTCH1 functions as a tumor suppressor. It is thought to have a repressive activity on cell proliferation and could play a role in DNA maintenance, repair and/or replication, since NBCSS syndrome is a chromosome instability syndrome.

Cancer-related alterations:

Germinal mutations lead to protein truncation in nevoid basal cell carcinoma syndrome (NBCCS) patients (see below); mutations types are variable: nucleotide substitutions (missense/nonsense), small deletions, or small insertions mainly, leading to protein truncation; these mutations have been observed in most exons; there is, so far, no mutation hot spot.

Somatic mutation and allele loss events have been observed in basal cell carcinoma, in NBCCS and in sporadic basal cell carcinoma. Mutation and allele loss have also been found in sporadic primitive neuroectodermal tumors (PNETs), sporadic medulloblastomas and in a few cases of esophageal squamous cell carcinoma and invasive transitional cell carcinoma of the bladder; mutations have also been reported in a low frequency of sporadic trichoepitheliomas (tumors often associated with basal cell carcinomas) and in sporadic odontogenic keratocysts
A large majority of these somatic mutations are substitutions. There are no mutation hot spots

Genetic alterations in PTCH1 are the cause of basal cell nevus syndrome (BCNS) also known as Gorlin syndrome or Gorlin-Goltz syndrome. BCNS is an autosomal dominant disease characterized by nevoid basal cell carcinomas (NBCCS) and developmental abnormalities such as rib and craniofacial alterations, polydactyly, syndactyly, and spina bifida. In addition, the patients suffer from a multitude of tumors like basal cell carcinomas (BCC), fibromas of the ovaries and heart, cysts of the skin, jaws and mesentery, as well as medulloblastomas and meningiomas. PTCH1 is also mutated in squamous cell carcinoma (SCC).

References (open access):

Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Lo Muzio L. Orphanet J Rare Dis. 2008 Nov 25;3:32.

Gorlin syndrome or basal cell nevus syndrome (BCNS): A case report. Shivaswamy KN, Sumathy TK, Shyamprasad AL, Ranganathan C. Dermatol Online J. 2010 Sep 15;16(9):6.

Mechanisms of inactivation of PTCH1 gene in nevoid basal cell carcinoma syndrome: modification of the two-hit hypothesis. Pan S, Dong Q, Sun LS, Li TJ. Clin Cancer Res. 2010 Jan 15;16(2):442-50.

Patched1 functions as a gatekeeper by promoting cell cycle progression. Adolphe C, Hetherington R, Ellis T, Wainwright B. Cancer Res. 2006 Feb 15;66(4):2081-8.


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