Disease relevance of Basal Cell Nevus Syndrome

• Mutations in the tumor suppressor gene PATCHED (PTC) are found in human patients with the basal cell nevus syndrome, a disease causing developmental defects and tumors, including basal cell carcinomas [1].
• Hemizygous Ptc1 mice have many features of Gorlin syndrome, including predisposition to medulloblastoma development [2].
• Germline mutations in the human homolog of the patched1 (PTCH1) are associated with basal cell nevus carcinoma syndrome (BCNS or Gorlin syndrome), which is characterized by developmental anomalies, radiation hypersensitivity and a predisposition to medulloblastomas and skin tumors [3].
• One hundred and twenty-four Australian patients with sporadic melanoma and 62 with familial basal cell carcinomas (a feature of nevoid basal cell carcinoma syndrome, NBCCS) were examined for germline homozygous deletions of GSTM1 using multiplex polymerase chain reactions [4].
• Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is an autosomal dominant disorder, characterized primarily by multiple basal cell carcinomas, epithelium-lined jaw cysts, and palmar and plantar pits, as well as various other features [5].

High impact information on Basal Cell Nevus Syndrome

• Topical 5-fluorouracil and the basal-cell-nevus syndrome [6].
• According to this model, the inhibition of SMO signalling is relieved following mutational inactivation of PTCH in basal-cell nevus syndrome [7].
• The PATCHED (PTC) gene encodes a Sonic hedgehog (Shh) receptor and a tumor suppressor protein that is defective in basal cell nevus syndrome (BCNS) [8].
• It is shown here that transgenic mice overexpressing SHH in the skin develop many features of basal cell nevus syndrome, demonstrating that SHH is sufficient to induce basal cell carcinomas in mice [1].
• Primary hyperparathyroidism and basal cell nevus syndrome [9].

Chemical compound and disease context of Basal Cell Nevus Syndrome

• Both tumors are associated with a deficiency in the tumor suppressor Patched (PTCH) in Gorlin syndrome (Gorlin, R. J. (1987) Medicine (Baltimore) 66, 98-113), and they are present in the corresponding murine models [10].
• Systemic retinoids are of little value in the treatment of premalignant and malignant cutaneous lesions though 13-cis-retinoic acid might be of use in the basal cell nevus syndrome [11].
• Failure of interferon alfa and isotretinoin combination therapy in the nevoid basal cell carcinoma syndrome [12].
• Long-term management of basal cell nevus syndrome with topical tretinoin and 5-fluorouracil [13].
• The recently discovered gene responsible for Gorlin syndrome, PTC (or PTCH), encodes a transmembrane protein with yet poorly known functions [14].

Biological context of Basal Cell Nevus Syndrome

• Individuals affected with the Gorlin syndrome inherit a germ-line mutation of the patched (Ptc1) developmental gene and, analogously to Ptc1 heterozygous mice, show an increased susceptibility to spontaneous tumor development [15].
• With identification of the Hedgehog receptor PTCH1 as a tumour suppressor gene that underlies the human nevoid basal cell carcinoma syndrome (NBCCS), the Hedgehog signalling pathway was firmly linked to cancer [16].
• Analysis of 133 meioses places the genes for nevoid basal cell carcinoma (Gorlin) syndrome and Fanconi anemia group C in a 2.6-cM interval and contributes to the fine map of 9q22.3 [17].
• In this collaborative study, an older mean paternal age has been documented in sporadic cases of at least five additional dominantly inheritable disorders; the basal cell nevus syndrome, the Waardenburg syndrome, the Crouzon syndrome, the oculo-dental-digital sysdrome, and the Treacher-Collins syndrome [18].
• Frequencies of spontaneous and radiation-induced chromosome aberrations were documented in lymphocytes from patients with basal cell nevus syndrome (BCNS) and from those with epidermodysplasia verruciformis (EV) [19].

Anatomical context of Basal Cell Nevus Syndrome

• Allele-discriminating oligonucleotide probes in conjunction with RCA also were used to discriminate wild-type and mutant alleles in the cystic fibrosis transmembrane conductance regulator, p53, BRCA-1, and Gorlin syndrome genes in the nuclei of cultured cells or in DNA fibers [20].
• In addition, basal cell nevus syndrome (BCNS), or Gorlin syndrome, which is characterized by developmental anomalies and a predisposition to skin and nervous system malignancies, is associated with germ-line mutation of ptc [21].
• To investigate the possible role of the PTC gene on chromosome 9q22.3, that was identified as the cause of nevoid basal cell carcinoma syndrome, during carcinogenesis in esophagus and lung, we examined 20 esophageal squamous cell carcinomas and 10 squamous cell carcinomas of the lung for mutations in any coding exon of PTC [22].
• Expression of cyclin D1 and p16 protein was detected in the basal and parabasal cells in lining epithelium of OKCs and was found more frequently in basal cell nevus syndrome (BCNS)-associated OKCs than in primary or recurrent OKCs [23].

Gene context of Basal Cell Nevus Syndrome

• The human growth-arrest-specific gene GAS1 maps outside the candidate region of the gene for nevoid basal cell carcinoma syndrome [24].
• In addition, dominant mutations of the XPAC and FACC1 genes can be ruled out as the cause of Gorlin syndrome, since the two patients described have null mutations [25].
• Interestingly, PTPH1 gene was mapped to 9q31 where the gene for Gorlin syndrome, a putative tumor suppressor gene, exists [26].
• Down-regulation of SMT3A gene expression in association with DNA synthesis induction after X-ray irradiation in nevoid basal cell carcinoma syndrome (NBCCS) cells [27].
• Mutations of the former cause the nevoid basal cell carcinoma syndrome (NBCCS) while mutations in the ROR2 gene have been found both in Robinow syndrome and in brachydactyly type 1B (BDB1) [28].

Analytical, diagnostic and therapeutic context of Basal Cell Nevus Syndrome

• Because the patient's seizures resolved after a modified left anterior temporal lobectomy, this case illustrates that epilepsy in patients with the nevoid basal-cell carcinoma syndrome is potentially curable and should be investigated appropriately [29].
• delta-Aminolevulinic acid and blue light photodynamic therapy for treatment of multiple basal cell carcinomas in two patients with nevoid basal cell carcinoma syndrome [30].
• To identify expressed sequences from the candidate genomic region of the nevoid basal cell carcinoma syndrome (9q22.3), the CpG island rescue PCR methodology was employed on the yeast artificial chromosome (YAC) ICI-8AD8 that contains microsatellite marker D9S180 [31].
• Aromatic retinoid in the chemoprevention of the progression of nevoid basal-cell carcinoma syndrome [32].

References