Fine Genetic Mapping of the Gene for Nevoid Basal Cell Carcinoma Syndrome

doi:10.1006/geno.1994.1423

Genomics

Volume 22, Issue 3, August 1994, Pages 505-511

https://doi.org/10.1006/geno.1994.1423 Get rights and content

Abstract

Nevoid basal cell carcinoma syndrome (NBCCS, or Gorlin syndrome) is a cancer predisposition syndrome characterized by multiple basal cell carcinomas and diverse developmental defects. The gene responsible for NBCCS, which is most likely to be a tumor suppressor gene, has previously been mapped to 9q22.3-q31 in a 12-cM interval between the microsatellite marker loci D9S12.1 and D9S109. Combined multipoint and haplotype analyses of additional polymorphisms in this region in our collection of Australasian pedigrees have further refined the localization of the gene to between the markers D9S196 and D9S180, an interval reported to be approximately 2 cM.

References (0)

Cited by (48)

Nonmelanoma Skin Cancers: Basal Cell and Squamous Cell Carcinomas
2019, Abeloff’s Clinical Oncology
This chapter of nonmelanoma skin cancers (NMSCs) provides an overview of most commonly seen skin cancers including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), as well as several rarer yet clinically concerning NMSCs including sebaceous carcinoma, Markel cell carcinoma, dermatofibrosarcoma protuberans and cutaneous angiosarcoma. Each of these neoplasms is discussed separately after a summary of genetic alterations in BCC, SCC, and selected genodermatoses. For each neoplasm, its epidemiology, etiology and biological characteristics, prevention and early detection, pathology and pathways of spread, clinical manifestations, patient evaluation and staging, primary therapy, treatment options for local advanced and metastatic disease, and challenges and future possibilities are described.
Nonmelanoma Skin Cancers: Basal Cell and Squamous Cell Carcinomas
2013, Abeloff's Clinical Oncology: Fifth Edition
Hereditary cancer syndromes of the skin
2005, Clinics in Dermatology
Hereditary cancer syndromes are a group of disorders characterized by a genetic susceptibility to the development of malignant tumors. Multiple cancers in the family or an abnormally early onset for the given cancer may suggest an underlying inherited predisposition. Awareness of their associated dermatologic manifestations can facilitate early detection of risk for neoplasms. This article provides an update on the clinical features, diagnostic criteria, and the use of genetic analysis in the detection of causative mutations of those hereditary cancer syndromes with cutaneous manifestations.
Differential modulation of Ku70/80 DNA-binding activity in a patient with multiple basal cell carcinomas
2003, Journal of Investigative Dermatology
Citation Excerpt :
Tumor samples were classified morphologically on the basis of growth pattern, as described previously (Jacobs et al, 1982;Rippey and Rippey, 1997). To exclude that the patient was affected by nevoid BCC syndrome, DNA extracted from fresh frozen tumor samples and blood lymphocytes was analyzed for loss of heterozygosity in microsatellite markers mapping on chromosome 9q near the nevoid BCC syndrome locus (Wicking et al, 1994). The following markers were tested: D9S196 (9q22); D9S197 (9q22.1); D9S180, D9S12, D9S287 (9q22,3); D9S109, D9S127 (9q31) (Farndon et al, 1992;Goldstein et al, 1994;Wicking et al, 1994).
Ku70/80 nonhomologous end-joining activity is essential for resolving random DNA double-strand breaks, and the Ku70/80 protein complex has been proposed as “caretaker” of genomic stability. We studied the Ku70/80 heterodimer activity in a patient affected by multiple basal cell carcinomas with a personal history of moderate exposure to ionizing radiation. The Ku70/80 DNA-binding activity was analyzed, by electrophoretic mobility shift assay, in five tumor biopsies from different sites and at distinct clinical stages, and in three matched normal skin samples from the same patient. As control normal tissues from healthy individuals were also tested. The five basal cell carcinomas were classified as “non aggressive” and “aggressive” on the basis of morphologic parameters and expression of the molecular markers bcl-2, Ki67/MIB1, and p53. A 62% increase in the Ku70/80 DNA-binding activity was found in normal skin from the patient, compared to unexposed individuals (p<0.0001). The nuclear activity of the heterodimer was further increased in nonaggressive basal cell carcinomas compared to both matched normal skin from the patient (31%, p=0.0001) and tissues from healthy controls (73%, p=0.0001). Strikingly, the two aggressive basal cell carcinomas tested showed very low Ku70/80 DNA-binding activity with a reduction of 87% compared to normal skin from the patient (p<0.0001) and 64% compared to controls (p=0.001). Although these results are limited to only one patient, together with other recent studies they support the hypothesis that downregulation of the nonhomologous end-joining pathway may be associated with tumor progression.
UV-specific p53 and PTCH mutations in sporadic basal cell carcinoma of sun-exposed skin
2001, Journal of the American Academy of Dermatology
UVB irradiation is known to produce DNA damage at mutation hotspots in the p53 tumor suppressor gene, leading to the development of skin cancers. Mutations in the PTCH tumor suppressor gene, which is known to be responsible for the development of nevoid basal cell carcinoma syndrome, have also been identified in sporadic basal cell carcinomas (BCCs). We describe the case of an 80-year-old welder in whom 3 novel p53 mutations, as well as UV-specific PTCH mutations, were detected in two BCC samples from sun-exposed skin. The simultaneous presence of UV-specific p53 and PTCH mutations in the same BCC sample has not previously been reported. (J Am Acad Dermatol 2001;44:293-7.)
Characterization of the mouse gene, human promoter and human cDNA of TSCOT reveals strong interspecies homology
2000, Biochimica et Biophysica Acta - Gene Structure and Expression
The regulation of gene expression in thymic epithelial cells is critical for T cell development. The mouse thymic epithelial gene Tscot encodes a protein with weak homology to bacterial 12 transmembrane co-transporters. Using competitive reverse transcription-polymerase chain reaction (RT-PCR), we show that low level Tscot expression is detectable in several other tissues. Tscot was mapped to chromosome 4 and was also detected in other mammalian species by Southern blotting. The human cDNA clone showed 77% amino acid identity with the mouse sequence. The highest conservation was in the TM regions and in a small segment of the central cytoplasmic loop. Genomic clones spanning 17 164 bases of the Tscot gene revealed four exons with nine of the TM domains encoded in the first exon. The major transcriptional start site in mouse was identified by a primer extension analysis and confirmed by RT-PCR. Comparison of 1.7 kb of the human and mouse promoters identified six conserved possible regulatory elements, one containing a potential binding site for an interferon α inducible factor. Finally, as a functional test, 3 kb of the murine promoter was used to create a transgenic mouse that expresses enhanced green fluorescent protein message strongly in the thymus, weakly in the kidney and undetectably in the spleen, liver and heart.

View all citing articles on Scopus

View full text

Regular ArticleFine Genetic Mapping of the Gene for Nevoid Basal Cell Carcinoma Syndrome

Abstract

Regular Article
Fine Genetic Mapping of the Gene for Nevoid Basal Cell Carcinoma Syndrome