PATCHED and p53 gene alterations in sporadic and hereditary basal cell cancer

Gao, Ling; Ahmadian, Afshin; Persson, Åsa; Undén, Anne Birgitte; Afink, Gijs B.; Williams, Cecilia; Uhlén, Mathias; Toftgárd, Rune; Lundeberg, Joakim; Pontén, Fredrik

doi:10.1038/sj.onc.1204946

Cited by 126 publications

(93 citation statements)

References 31 publications

(31 reference statements)

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“…Most BCC tumors have PTCH1 gene inactivating mutations that cause Shh signaling to be activated constitutively (Aszterbaum et al, 1998;Johnson et al, 1996;Ling et al, 2001;Xie et al, 1998). In general, more than 70% of sporadic BCCs have detectable genetic mutations in components of the Shh signaling pathway that lead to elevated levels of the Gli1 transcription factor (Dahmane et al, 1997;Ling et al, 2001).…”

Section: Basal Cell Nevus Syndrome and Ptch1 Heterozygous (+/−) Micementioning

confidence: 99%

“…In general, more than 70% of sporadic BCCs have detectable genetic mutations in components of the Shh signaling pathway that lead to elevated levels of the Gli1 transcription factor (Dahmane et al, 1997;Ling et al, 2001). Patients with Basal Cell Nevus Syndrome (BCNS or Gorlin syndrome, MIM # 109400), a rare multi-system disease whose hallmark is the development of dozens to thousands of BCCs, inherit one defective copy of PTCH1 and lose the other copy somatically in tumors.…”

Section: Basal Cell Nevus Syndrome and Ptch1 Heterozygous (+/−) Micementioning

confidence: 99%

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Novel Hedgehog pathway targets against basal cell carcinoma

Tang

Epstein

2007

Toxicology and Applied Pharmacology

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The Hedgehog signaling pathway plays a key role in directing growth and patterning during embryonic development and is required in vertebrates for the normal development of many structures, including the neural tube, axial skeleton, skin, and hair. Aberrant activation of the Hedgehog (Hh) pathway in adult tissue is associated with the development of basal cell carcinoma (BCC), medulloblastoma, and a subset of pancreatic, gastro-intestinal, and other cancers. This review will provide an overview of what is known about the mechanisms by which activation of Hedgehog signaling leads to the development of BCCs and will review two recent papers suggesting that agents that modulate sterol levels might influence the Hh pathway. Thus, sterols may be a new therapeutic target for the treatment of BCCs, and readily available agents such as statins (HMG-CoA reductase inhibitors) or vitamin D might be helpful in reducing BCC incidence. Epidemiology of Basal cell carcinoma (BCC)Basal cell carcinoma (BCC), the most common of all human cancers, affects close to 1 million Americans a year. Over the past 40 years there has been a dramatic increase in the incidence of BCC, and it is estimated that nearly 30% of Caucasians living in areas of high ambient sun exposure will develop a BCC (Miller and Weinstock, 1994). Furthermore, the incidence of BCC is rising in younger populations, especially among women (Christenson et al., 2005). Although the case fatality rate of BCCs is low, the high incidence and frequent occurrence of multiple primary tumors in affected individuals leads to significant morbidity. BCCs characteristically arise in sun-exposed body areas, most commonly on the head and neck, but also occur on the trunk and extremities. There are three accepted environmental insults for BCC development: ultraviolet radiation (UV), ionizing radiation (IR), and arsenic. Interindividual differences in the susceptibility to BCC development have been recognized for many years. Epidemiologic studies have identified phenotypic features such as fair skin and freckling tendency that are associated with an increased susceptibility to BCCs (Rubin et al., 2005).It is generally accepted that BCC can be caused by UV exposure from the sun. While the risk of squamous cell carcinoma is strongly related to cumulative sun exposure, sunlight's exact role in BCC development remains less clear (Armstrong and Kricker, 2001). Thus, epidemiologic studies have shown that BCC risk correlates better with intermittent sun exposure (i.e. childhood sunburns, weekend sun exposure) than with cumulative lifetime sun exposure (Corona et al., 2001). Hence, the timing, dose, and duration of UV exposure are critical to carcinogenesis, but UV seems to have a different role in SCC versus BCC carcinogenesis development. Consistent with this, a randomized clinical trial of daily sunscreen use showed that sunscreen reduced the incidence of SCC but not BCC. The daily application of an SPF 15 sunscreen to the head, neck, arms, and hands over a 4-5 year period had no e...

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Section: Basal Cell Nevus Syndrome and Ptch1 Heterozygous (+/−) Micementioning

confidence: 99%

Section: Basal Cell Nevus Syndrome and Ptch1 Heterozygous (+/−) Micementioning

confidence: 99%

Novel Hedgehog pathway targets against basal cell carcinoma

Tang

Epstein

2007

Toxicology and Applied Pharmacology

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“…72,73 Finally, it is noteworthy that about 30% of those with NBCCS have mutations in p53. 74 I am most pleased with the notion of Editor-in-Chief, Dr. Richard King and his staff, to invite a number of individuals to tell "how it all began." These tales often involve serendipity, as it did in the case of nevoid basal cell carcinoma syndrome.…”

Section: Geneticsmentioning

confidence: 99%

Nevoid basal cell carcinoma (Gorlin) syndrome

Gorlin

2004

Genetics in Medicine

322

191

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“…[1][2][3] Both tumors are strongly associated with chronic ultraviolet (UV) radiation exposure and occur primarily, but not exclusively, on sun-exposed areas of the body. [4][5][6][7][8] The most commonly mutated gene in basal cell carcinoma and squamous cell carcinoma is TP53, with the majority of mutations consistent with UV as the mutagen. 9,10 Inactivating mutations in the PTCH gene, the gene responsible for nevoid basal cell carcinoma syndrome, have also been identified in sporadic basal cell carcinoma, also with evidence for UV causation.…”

mentioning

confidence: 99%

Mutations of the TERT promoter are common in basal cell carcinoma and squamous cell carcinoma

2014

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Telomerase is frequently expressed in cancer and contributes to carcinogenesis. Two recent publications report the identification of a set of recurrent mutations in melanoma in the promoter of the telomerase reverse transcriptase gene (TERT) that appears to be the result of mutagenesis from ultraviolet (UV) radiation. Both groups reported that the mutations increase the transcription of TERT. This prompted our search for similar mutations in two other UV-related skin cancers, basal cell carcinoma, and squamous cell carcinoma. We found that the activating TERT promoter mutations reported in melanoma are also frequent in squamous cell carcinoma (50%) and basal cell carcinoma, the latter including both sporadic tumors (78%) and tumors from patients with nevoid basal cell carcinoma syndrome (68%). These mutations were found in only 1 of 11 Bowen's disease (squamous cell carcinoma in situ) specimens, and in none of 15 non-malignant skin specimens and 57 blood specimens. The mutations were frequently homozygous or hemizygous, with little or no normal signal at the mutated positions. These data suggest that TERT promoter mutations are the most frequent putative oncogenic mutations in cutaneous cancer.

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PATCHED and p53 gene alterations in sporadic and hereditary basal cell cancer

Cited by 126 publications

References 31 publications

Novel Hedgehog pathway targets against basal cell carcinoma

Novel Hedgehog pathway targets against basal cell carcinoma

Nevoid basal cell carcinoma (Gorlin) syndrome

Mutations of the TERT promoter are common in basal cell carcinoma and squamous cell carcinoma

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