<i>PTCH</i> germline mutations in Chinese nevoid basal cell carcinoma syndrome patients

Li, T. J.; Yuan, Jing; Gu, Xiaomei; Sun, Lisha; Zhao, Huaxiang

doi:10.1111/j.1601-0825.2007.01369.x

Cited by 25 publications

(21 citation statements)

References 27 publications

(43 reference statements)

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“…Of the six mutations identified, five (c. 403C>T, c.1012C>T, c.2179delT, c.2824delC, c.3162dupG) resulted in truncation of the PTCH protein. These results were in consistent with the previous reports that most PTCH mutations lead to a premature termination of the protein (Li et al, 2008;Wicking et al, 1997) .…”

Section: Discussionsupporting

confidence: 83%

“…So far, several studies have provided evidence that PTCH might take part in the pathogenesis of NBCCS-associated and sporadic KCOTs (Barreto et al, 2000;Gu et al, 2006;Sun et al, 2008). In this study, we identified 6 additional PTCH mutations in 2 out of 8 sporadic and 3 out of 4 NBCCS-associated KCOTs, consisted of 2 nonsense, 3 frameshift and 1 inframe duplication mutations.…”

Section: Discussionmentioning

confidence: 68%

“…All 23 exons and the exon-intron boundaries of the PTCH gene were amplified by polymerase chain reaction (PCR) with specific primers described previously (Gu et al, 2006;Sun et al, 2008). PCR was performed in a volume of 50 μL containing 100 ng of DNA, 10 pmol/L of each primer, 2.5 mmol/L of dNTPs, 1 unit of Taq DNA polymerase in PCR buffer.…”

Section: Dna Extraction and Polymerase Chain Reactionmentioning

confidence: 99%

“…The majority of KCOTs arise sporadically in single form while multiple lesions often occur when associated with NBCCS. It has been reported that nearly 75% NBCCS-associated KCOTs harbored PTCH mutations, while only a few reports documented PTCH mutations in Chinese patients with sporadic KCOTs (Gu et al, 2006;Sun et al, 2008). The aim of this study was to search for PTCH mutations in both nonsyndromic and syndrome-associated KCOTs.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of Known and Novel PTCH Mutations in Both Syndromic and Non‐syndromic Keratocystic Odontogenic Tumors

Pan

Sun

et al. 2009

Int J Oral Sci

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 68%

Section: Dna Extraction and Polymerase Chain Reactionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of Known and Novel PTCH Mutations in Both Syndromic and Non‐syndromic Keratocystic Odontogenic Tumors

Pan

Sun

et al. 2009

Int J Oral Sci

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“…However, the original references on mutations were all on syndromic patients and the 6 WHO references on non-syndromic cases included syndromic patients. There were numerous subsequent papers dealing with PTCH mutations in syndromic and nonsyndromic OKCs, which have shown mutations in approximately 85 % of syndromic cases and 30 % of non-syndromic cases [26][27][28][29][30][31][32].…”

Section: The Cyst/neoplasm Interfacementioning

confidence: 99%

Odontogenic Tumors, WHO 2005: Where Do We Go from Here?

Wright

Odell

Speight

et al. 2014

Head and Neck Pathol

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Heterozygous PTCH1 Mutations Impact the Bone Metabolism in Patients With Nevoid Basal Cell Carcinoma Syndrome Likely by Regulating SPARC Expression

Hong

Zhang

et al. 2016

Journal of Bone and Mineral Research

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Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by bone and skin abnormalities and a predisposition to various tumors. Keratocystic odontogenic tumors (KCOTs), which are common tumors of the jaw that cause extensive damage to the jawbone, are usually accompanied with NBCCS. Germline PTCH1 mutations in NBCCS tumorigenesis have been frequently studied; however, little is known regarding the pathogenesis of bone abnormalities in this disease. This study sought to investigate the mechanism underlying heterozygous PTCH1 mutation-mediated abnormal bone metabolism in patients with NBCCS. Stromal cells were isolated from the fibrous capsules of patients with NBCCS-associated or non-syndromic keratocystic odontogenic tumors and non-syndromic tumor stromal cells without PTCH1 mutations served as controls. Germline PTCH1 heterozygous mutations were confirmed in all NBCCS samples and differential protein expression was identified using tandem mass tag-labeled proteomics analysis. Our findings revealed that osteonectin/SPARC expression was significantly downregulated in syndromic stromal cells compared with non-syndromic stromal cells. SPARC expression was even lower in stromal cells carrying PTCH1 protein truncation mutations. PTCH1 siRNA transfection demonstrated that SPARC downregulation correlates with decreased PTCH1 expression. Furthermore, exogenous SPARC promoted osteogenic differentiation of syndromic stromal cells with enhanced development of calcium nodules. In addition, bone mineral density tests showed that patients with NBCCS exhibit weak bone mass compared with sex-and age-matched controls. This study indicates that germline PTCH1 heterozygous mutations play a major role in bone metabolism in patients with NBCCS, in particular in those with PTCH1 protein truncation mutations. SPARC may represent an important downstream modulator of PTCH1 mediation of bone metabolism. Thus, bone mineral density monitoring is critical for patients with NBCCS for prevention of osteoporosis. In addition, surgical procedures on syndromic-associated KCOTs should be performed with consideration of the weaker bone mass in such patients.

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PTCH germline mutations in Chinese nevoid basal cell carcinoma syndrome patients

Abstract: The frequent germline PTCH mutations detected in our series provide further evidence for the crucial role of PTCH in the pathogenesis of nevoid basal cell carcinoma syndrome in Chinese.

Cited by 25 publications

References 27 publications

Identification of Known and Novel PTCH Mutations in Both Syndromic and Non‐syndromic Keratocystic Odontogenic Tumors

Identification of Known and Novel PTCH Mutations in Both Syndromic and Non‐syndromic Keratocystic Odontogenic Tumors

Odontogenic Tumors, WHO 2005: Where Do We Go from Here?

Heterozygous PTCH1 Mutations Impact the Bone Metabolism in Patients With Nevoid Basal Cell Carcinoma Syndrome Likely by Regulating SPARC Expression

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