A novel PTCH1 mutation in a patient of nevoid basal cell carcinoma syndrome

Honma, Masaru; Ohishi, Yasushi; Uehara, Jiro; Ibe, Masaki; Kinouchi, Motoshi; Ishida‐Yamamoto, Akemi; Iizuka, Hajime

doi:10.1016/j.jdermsci.2007.10.009

Cited by 5 publications

(3 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To better understand the pathogenesis of the spontaneous BCCs in our Ptch1 +/− /SKH-1 mice, we analyzed mutations in the tumor suppressor genes Ptch1 and p53. Humans with NBCCS inherit a germline mutation in one allele of the Ptch1 gene and tumor development is generally accompanied by loss of the remaining wild-type allele leading to aberrant activation of Shh signaling that drives the growth of these lesions [ 9 , 11 , 12 , 16 ]. Here, we detected multiple Ptch1 mutations in spontaneous BCCs from Ptch1 +/− /SKH-1 hairless mice ( Supplemental Figure S6 ) which were similar to those known to occur in NBCCS patients [ 51 ].…”

Section: Resultsmentioning

confidence: 99%

Shh and p50/Bcl3 signaling crosstalk drives pathogenesis of BCCs in gorlin syndrome

et al. 2015

View full text Add to dashboard Cite

Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disorder that is due, in large measure, to aberrant Shh signaling driven by mutations in the tumor suppressor gene Ptch1. Here, we describe the development of Ptch1+/−/SKH-1 mice as a novel model of this disease. These animals manifest many features of NBCCS, including developmental anomalies and are remarkably sensitive to both ultraviolet (UVB) and ionizing radiation that drive the development of multiple BCCs. Just as in patients with NBCCS, Ptch1+/−/SKH-1 also spontaneously develops BCCs and other neoplasms such as rhabdomyomas/rhabdomyosarcomas. Administration of smoothened inhibitors (vismodegib/itraconazole/cyclopamine) or non-steroidal anti-inflammatory drug (sulindac/sulfasalazine) each result in partial resolution of BCCs in these animals. However, combined administration of these agents inhibits the growth of UVB-induced BCCs by >90%. Employing small molecule- and decoy-peptide-based approaches we further affirm that complete remission of BCCs could only be achieved by combined inhibition of p50-NFκB/Bcl3 and Shh signaling. We posit that Ptch1+/−/SKH-1 mice are a novel and relevant animal model for NBCCS. Understanding mechanisms that govern genetic predisposition to BCCs should facilitate our ability to identify and treat NBCCS gene carriers, including those at risk for sporadic BCCs while accelerating development of novel therapeutic modalities for these patients.

show abstract

Section: Resultsmentioning

confidence: 99%

Shh and p50/Bcl3 signaling crosstalk drives pathogenesis of BCCs in gorlin syndrome

et al. 2015

View full text Add to dashboard Cite

show abstract

“…11 All available PTCH1 molecular data of the Japanese BCNS patients also indicated a dispersed distribution of mutations in all regions and suggested no founder effect (Table 3). 16,[18][19][20][21][22][23][24][25][26] The typical symptoms of the Japanese BCNS patients are characterized by palmar and plantar pits, odontogenic keratocysts and abnormal skeletons and are sometimes accompanied by BCC, especially in elderly patients. On the other hand, BCC is observed at a frequency of up to 97% in Caucasian BCNS patients with the same symptoms as the Japanese.…”

Section: Discussionmentioning

confidence: 99%

Germline PTCH1 mutations in Japanese basal cell nevus syndrome patients

et al. 2009

View full text Add to dashboard Cite

“…15,[17][18][19][20][21][22][23][24][25][26][27][28] Table 3 summarizes the spectrum of PTCH1 mutations and phenotypes of Japanese NBCCS patients. Overall 56 subjects who fulfilled the criteria for NBCCS were analyzed.…”

Section: Minor Symptomsmentioning

confidence: 99%