PTCH was recently proposed as a candidate gene for NBCCS due to its frequent mutation in basal cell carcinomas, the cancer most often associated with this syndrome.
Frequent allelic losses on chromosome 9 are seen in a wide variety of human tumors; moreover, two genes (P16 and PTC) whose mutant alleles confer predispositions to some inherited cancer syndromes have been identified on this chromosome.
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.
The results indicate that RT-PCR for ret/PTC is a specific marker that can be applied to fine needle aspiration biopsies and improves the diagnosis of malignancy when used as an adjunct to traditional cytology.
Assessment of RET/PTC oncogene activation and clonality in thyroid nodules with incomplete morphological evidence of papillary carcinoma: a search for the early precursors of papillary cancer.
Basal cell carcinoma (BCC), the most common form of human cancer, is understood to be associated with activation of the sonic hedgehog pathway, through loss-of-function mutations of tumor suppressor PTCH1 or gain-of-function mutations of smoothened.
Many of these mutations, including ptc1-Q688X, result in premature truncation of the ptc1 protein. ptc1-Q688X has been identified in patients with both BCC and nevoid basal cell carcinoma syndrome, an inheritable disorder causing a predisposition to cancer susceptibility.
The sonic hedgehog (Shh) transcript is localized to the cancer tissue, whereas expression of Gli1 and PTCH1 is observed both in the cancer and in the surrounding stroma.
Correspondingly, expression of GLI1, a transcription factor and transcriptional product of hedgehog signaling, was increased 8-fold in cancer epithelial cell lines; however, PTCH1, also a transcriptional target of hedgehog signaling in many cell types, was not increased.
BRAF or RET/PTC mutations were always associated with cancer, whereas RAS mutations were mainly associated with cancer (74%) but also follicular adenoma (26%).
Basal cell carcinoma (BCC) of the skin is the most common form of cancer, with the majority being caused by mutations in the Patched1 (Ptch1) gene, leading to activation of the Hedgehog (Hh) signaling pathway.
PTCH and BMP4 mRNA levels as well as MUC5AC were significantly increased only in the control group and were significantly higher in the controls than those in the cancer group after eradication.
Sunitinib is currently being evaluated in advanced human thyroid carcinomas, based on the rationale that the vascular endothelial growth factor and platelet-derived growth factor receptors and the RET/PTC rearrangement are valuable targets for the treatment of this malignancy.
While the presence of a BRAF and RET/PTC mutation was associated with cancer in 100% of samples each, the presence of a RAS and PAX8/PPARG mutation was associated with cancer in only 12% and 50% of samples, respectively.
Our finding of tumor-specific patterns of NR expression, as well as significant differences in NR expression between BRAF(V600E) and wild type BRAF PTC, provides a basis for further mechanistic studies and highlights potential novel therapeutic targets for this malignancy.
Mutations in the transmembrane receptor patched homolog 1 (Homo sapiens) (ptch1) are responsible for nevoid basal cell carcinoma syndrome (NBCCS), an autosomal dominant disorder that causes developmental abnormalities and predisposes the affected individuals to cancer.
By analyzing RNA-sequencing based transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression--as a hallmark of the canonical Hh-pathway activity in this malignancy.
For our primary cohort, the preceding FNA diagnosis associated with the highest risk of malignancy was suspicious for PTC in nearly half (48.6%) of cases.
Patients in the PTC-EFB group had higher preoperative bilirubin (243 versus 169 μmol/l, p = 0.005) and a higher incidence of malignancy (87% versus 67%, p = 0.008).