5727

PTCH1

patched 1;PTCH1;patched 1

PTCH protein +12b|PTCH protein +4'|PTCH protein -10|PTCH protein -3,4,5|protein patched homolog 1

9q22.3

protein-coding

Basal cell carcinosarcoma is a rare biphenotypic malignant skin tumor, in which one tumor component has light microscopic features of basal cell carcinoma, whereas the other has features of sarcoma. Clinical experience with this tumor is limited, and associated molecular genetic alterations are unknown. Herein, we report a unique case of metastatic basal cell carcinosarcoma, in which we analyzed the 2 components of the primary tumor as well as the metastasis by next-generation sequencing. The patient was a 72-year-old man who presented with a 7-year history of a large tumor of the left forearm. The tumor showed mixed features of basal cell carcinoma and undifferentiated sarcoma. The patient underwent a wide local excision and sentinel lymph node biopsy, which revealed microscopic subcapsular deposits of metastatic sarcomatoid tumor. One year later, intra-abdominal metastatic tumor was detected and resected. It had sarcomatoid features by light microscopy and failed to stain for epithelial markers by immunohistochemistry. DNA was extracted separately from the epithelial and sarcomatoid component of the primary tumor, intra-abdominal metastasis, and normal tissue. All exons of 230 cancer-associated genes were sequenced to an average read depth of >500-fold. This revealed multiple identical mutations in epithelial and sarcomatoid tumor compartments. Both compartments harbored 2 identical mutations, a truncating and a missense mutation, in the patched gene (PTCH1). This finding is not only of interest for a shared heritage of different subpopulations in a biphenotypic tumor, but also relevant clinically. It provides a rationale for the clinical use of hedgehog pathway inhibitors for treatment of patients affected by this tumor. Unfortunately, the patient reported herein died of metastatic disease before targeted therapy could be initiated.

PURPOSE: The activation of hedgehog (Hh) pathways has been studied extensively in many malignant tumors to elucidate their clinical diagnostic and prognostic utilities. However, their roles in primary gallbladder carcinoma (GBC) remain poorly understood. This study was conducted to clarify the immunoreactivity and prognostic value of Hh pathway components in GBC. METHODS: Levels of sonic hedgehog (Shh), its receptor, Patched (Ptch1), and its downstream transcription factor, Gli1 protein, were measured by immunohistochemistry in 93 specimens from patients with GBC. We analyzed the correlations between the expression of these factors and clinicopathological features, including prognosis. RESULTS: Among the 93 GBC specimens, 76 (81.7%), 70 (75.3%) and 66 (70.0%) were positive for Shh, Ptch1 and Gli1 expression, respectively. expressions were significantly correlated with stage, lymph node metastasis, venous invasion, hepatic infiltration and lymphatic invasion (all P < 0.05). Patients with positive staining for Shh, Ptch1 and Gli1 had significantly lower survival rates than patients with negative staining. The expression patterns of Shh, Ptch1 and Gli1 were all associated with a malignant behavior risk category in GBC. CONCLUSIONS: To our knowledge, this is the first report to define the role of the Hh pathway in GBC. Shh, Ptch1 and Gli1 are frequently expressed in GBC and associated with poorer survival. Thus, high expressions of Shh, Ptch1 and Gli1 proteins could serve as auxiliary parameters for predicting the malignant behavior of GBC.

BACKGROUND: microRNAs (miRNAs) are a class of small non-coding RNAs that play important roles in carcinogenesis. In the present study, we investigated the effect of miR-212 on pancreatic ductal adenocarcinoma (PDAC) and its target protein. METHODS: Quantitative real-time PCR(qRT-PCR) was performed to detect the expression of miR-212 in PDAC tissues and pancreatic cancer cell lines. miR-212 mimic, miR-212 inhibitor and negative control were transfected into pancreatic cancer cells and the effect of miR-212 up-regulation and down-regulation on the proliferation, migration and invasion of cells were investigated. Furthermore, the mRNA and protein levels of Patched-1(PTCH1) were measured. Meanwhile, luciferase assays were performed to validate PTCH1 as miR-212 target in PDAC. RESULTS: miR-212 was up-regulated in PDAC tissues and cells.Using both gain-of function and loss-of function experiments, a pro-oncogenic function of miR-212 was demonstrated in PDAC. Moreover, up-regulated of PTCH1 could attenuate the effect induced by miR-212. CONCLUSION: These data suggest that miR-212 could facilitate PDAC progression and metastasis through targeting PTCH1, implicating a novel mechanism for the progression of PDAC.