Mutations in BHD and TP53 genes, but not in HNF1β gene, in a large series of sporadic chromophobe renal cell carcinoma
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ABSTRACT:
SUBMITTER: Gad S
PROVIDER: S-EPMC2366539 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BHD, TP53, and HNF1beta on chromosome 17 were studied in 92 cases of renal cell carcinoma (46 chromophobe, 19 clear cell, 18 oncocytoma, and nine papillary). Six, thirteen, and zero cases had, respectively BHD, TP53, and HNF1beta mutations, (84% mutations involved chromophobe), suggesting a role for BHD and TP53 in chromophobe subtype.
| S-EPMC2360004 | biostudies-literature
Project description:BACKGROUND:The purpose of the study was to evaluate clinical features and prognostic factors in a large single institutional cohort of chromophobe renal cell carcinoma (ChRCC) patients for identification of tumors with the highest metastatic potential. PATIENTS AND METHODS:Clinicopathological parameters of all patients with ChRCC diagnosed and surgically treated at Memorial Sloan Kettering Cancer Center between 1990 and 2016 were identified and compared with patients treated for clear-cell renal cell carcinoma (ccRCC) in the same study period using Wilcoxon test for continuous variables and Fisher exact test for categorical variables. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method, log rank test, and Cox proportional hazards regression. RESULTS:Four hundred ninety-six patients with ChRCC (10-year RFS, 91.7% and OS, 82.1%) and 3312 patients with ccRCC (10-year RFS, 79.4% and OS, 63.6%) were included in the analysis. Patients with ChRCC were younger (median 59 vs. 61 years; P = .0015), less frequently male (54.8% vs. 66.3%; P < .0001), showed more favorable T stages (T1-2 in 78% vs. 67%; P < .0001) and less frequent sarcomatoid differentiation (1.2 % vs. 4%; P = .0008) and showed lower rates of metastatic development compared with ccRCC patients. Larger tumor size, sarcomatoid differentiation, and higher T-stage are significantly associated with adverse RFS and OS in chromophobe tumors. CONCLUSION:ChRCC is more commonly diagnosed in female and younger patients and is associated with a more favorable clinical outcome and a lower propensity for metastatic development than ccRCC. Larger tumors and sarcomatoid differentiation of ChRCC might be considered as risk factors for metastatic development.
| S-EPMC6790280 | biostudies-literature
Project description:Germline mutations in the BHD gene cause the dominantly inherited cancer susceptibility disorder, Birt-Hogg-Dubé (BHD) syndrome. Individuals with BHD are reported to have an increased risk of renal cell carcinoma (RCC) and of colorectal polyps and cancer. The BHD gene maps to 17p11.2, and to investigate whether somatic inactivation of the BHD gene region is implicated in the pathogenesis of sporadic RCC and colorectal cancer (CRC), we performed mutation analysis in 30 RCC primary tumours and cell lines, and 35 CRCs and cell lines. A somatic missense mutation (Ala444Ser) with loss of the wild type allele (consistent with a two hit mechanism of tumorigenesis) was detected in a primary clear cell RCC, and a further missense mutation (Ala238Val) was identified in a clear cell RCC cell line for which matched normal DNA was not available. A somatic missense substitution (Arg392Gly) was identified in a primary CRC, and the same change was detected in three RCCs (all oncocytomas) for which matched normal DNA was not available. A germline Arg320Gln missense variant detected in a primary CRC was not detected in 40 control individuals or in a further 159 familial and sporadic CRC cases. However, AA homozygotes for an intronic single nucleotide polymorphism (c.1517+6 G-->A) were under-represented in familial cases compared with controls (p = 0.03). For some tumour suppressor genes, epigenetic silencing is a more common mechanism of inactivation than somatic mutations. However, we did not detect evidence of epigenetic silencing of BHD in 19 CRC and RCC cell lines, and BHD promoter region hypermethylation was not detected in 20 primary RCCs. These findings suggest that BHD inactivation occurs in a subset of clear cell RCC and CRC.
| S-EPMC1735328 | biostudies-other
Project description:Each histological variant of renal cell tumors has a unique color. The yellowish color of clear cell renal cell carcinoma (CCRCC) is explained by the presence of intracytoplasmic lipid and glycogen accumulation. Color changes in CCRCC are correlated with clinicopathological and metabolic changes, as well as biological behavior. We analyzed and compared the clinical, histopathological, and immunohistochemical features and gene expression profiles, in lipid metabolism of yellowish-colored ChRCC (ChRCC-Y), non-yellowish-colored ChRCC (ChRCC-N), and CCRCC. Of 14 ChRCCs, we retrieved 6 ChRCC-Ys. Patients with ChRCC-Y are younger than those with ChRCC-N, and the tumor is not predominant in males. ChRCC-Ys are smaller than ChRRC-Ns. Three ChRCC-Ys exhibited individual discrete tubule formation. No ChRCC-Ns exhibited individual discrete tubule formation. Two of 6 ChRCC-Ys showed relatively diffuse adipophilin positivity. No ChRCC-Ns demonstrated diffuse positivity for adipophilin. The expression of SCD, FDFT1, and E2F1 showed a tendency to be lower in ChRCC-Y than in ChRCC-N. The expression of PDGFB showed a tendency to be higher in ChRCC-Y than in ChRCC-N. This study demonstrated ChRCC-Y did not indicate an increase in lipid and cholesterol metabolism and that ChRCC-Y did not have the common molecular alteration of CCRCC. The absence of such metabolic acceleration in ChRCC-Y might support the biological indolent behavior. Furthermore, we revealed that macroscopic color changes might be correlated with various clinicopathological features and immunohistochemical and molecular changes from different perspectives. We believe further characterization of RCC, including tumor heterogeneity, is needed to improve the management of patients with RCC.
| S-EPMC8671824 | biostudies-literature
Project description:Background:The various pathogenesis between Clear cell renal carcinoma (CCRCC) and Chromophobe renal carcinoma (CHRCC) contributes to the different tumor growth rate and metastasis. In this study, we explored the distinct proteomic profiles between these two cancers and found different expression of glycogen phosphorylases in two cancers. Methods:We explored novel targets by proteomics. Five CCRCC cases and five CHRCC cases were selected for tandem mass tag-labeling liquid chromatography-mass spectroscopy (LC-MS). Gene ontology and KEGG pathway were applied for bioinformatic analysis. Glycogen phosphorylases were detected by Western blotting. Results:CHRCC were younger, more commonly female, and had larger tumors compared to those with CCRCC. 101 differentially expressed proteins (DEPs) in CCRCC and 235 DEPs in CHRCC were detected by LC-MS. It was found that disruption of metabolic pathways, epithelial cell differentiation, and cell response were the common characters for two tumor types. Activation of cell-cell adhesion and oxidation-reduction process stimulate CCRCC growth and epithelial cell differentiation and transferrin transport was involved in CHRCC growth, We also found that oxidative phosphorylation is activated in CHRCC and inhibited in CCRCC. More importantly, we found and confirmed that upregulation of glycogen phosphorylase liver type in CCRCC and glycogen phosphorylase brain type in CHRCC mediated differential glycogenolysis in the two tumor types, which could serve as potential therapeutic targets. Conclusion:We found different expression of glycogen phosphorylases in CCRCC and CHRCC by quantitative proteomics, which provides potential therapeutic targets in the future.
| S-EPMC7043045 | biostudies-literature
Project description:We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.
| S-EPMC4160352 | biostudies-literature
Project description:Past research on pathogenesis of a complex disease suggests that differentially expressed message RNAs (mRNAs) can be noted as biomarkers of a disease. However, significant miRNA-mediated regulation change might also be more deep underlying cause of a disease. In this study, a miRNA-mediated regulation module is defined based on GO terms (Gene Ontology terms) from which dysfunctional modules are identified as the suspected cause of a disease. A miRNA-mediated regulation module contains mRNAs annotated to a GO term and MicroRNAs (miRNAs) which regulate the mRNAs. Based on the miRNA-mediated regulation coefficients estimated from the expression profiles of the mRNA and the miRNAs, a SW (single regulation-weight) value is then designed to evaluate the miRNA-mediated regulation change of an mRNA, and the modules with significantly differential SW values are thus identified as dysfunctional modules. The approach is applied to Chromophobe renal cell carcinoma and it identifies 70 dysfunctional miRNA-mediated regulation modules from initial 4381 modules. The identified dysfunctional modules are detected to be comprehensive reflection of chromophobe renal cell carcinoma. The proposed approach suggests that accumulated alteration in miRNA-mediated regulation might cause functional alterations, which further cause a disease. Moreover, this approach can also be used to identify diffentially miRNA-mediated regulated mRNAs showing more comprehensive underlying association with a disease than differentially expressed mRNAs.
| S-EPMC4892590 | biostudies-literature
Project description:IntroductionChromophobe renal cell carcinoma, a distinct subtype of renal cell carcinoma (RCC) with characteristic light microscopic, histochemical, and ultrastructural features, typically has a favorable clinical course.Presentation of caseA 45-year-old femele presented with abdominal pain. A physical examination found a palpable mass in the left upper quadrant of the abdomen. A CT scan of the abdomen showed a heterogeneously enhancing mass, with necrosis and calcifications contents betwen the liver and the right kidney. she underwent surgical resection. Partial nephrectomy was performed. Pathological diagnosis was Chromophobe renal cell carcinoma.Discussion and conclusionChromophobe RCC is a rare variety of kidney neoplasm that has recently been better characterized from a molecular and genetic perspective. Overall, it is considered to have a better prognosis, and is associated with earlier stage tumors and longer overall survival compared with clear cell RCC.
| S-EPMC8350170 | biostudies-literature
Project description:Renal cell carcinoma (RCC) is a histopathologically and molecularly heterogeneous disease with the chromophobe subtype (chRCC) accounting for approximately 5% of all cases. The median overall survival of advanced RCC has improved significantly since the advent of tyrosine kinase inhibitors and mammalian target of rapamycin (mTOR) inhibitors. However, high-quality evidence for the use of new generation tyrosine kinase inhibitors in patients with advanced chRCC is lacking. Few published case reports have highlighted the use of temsirolimus in chRCC.Here, we report the case of a 36-year-old Caucasian woman with metastatic chRCC with predominantly skeletal metastases who was refractory to sunitinib who demonstrated a durable clinical response to temsirolimus lasting 20 months. We review the available evidence pertaining to the use of new generation molecularly targeted agents, in particular mTOR inhibitors in chRCC and discuss their emerging role in the management of this disease which would aid the oncologists faced with the challenge of treating this rare type of RCC.Conducting randomised clinical trials in this rarer sub-group of patients would be challenging and our case report and the evidence reviewed would guide the physicians to make informed decision regarding the management of these patients.
| S-EPMC3679738 | biostudies-other
Project description:Background: Clear cell renal cell carcinoma (ccRCC) and chromophobe renal cell carcinoma (chRCC) can usually be distinguished by histologic characteristics. Occasionally, diagnosis proves challenging and diagnostic difficulty will likely increase as needle biopsies of renal lesions become more common. Method: To identify markers that aid in differentiating ccRCC from chRCC, we used gene expression profiles to identify candidate markers that correlate with histology. 39 antisera and antibodies, including 35 for transcripts identified from gene expression profiling, were evaluated. Promising markers were tested on a tissue microarray (TMA) containing 428 renal neoplasms. Strength of staining of each core on the TMA was formally scored and the distribution of staining across different types of renal neoplasms was analyzed. Results: Based on results from initial immunohistochemical staining of multitissue titer arrays, 23 of the antisera and antibodies were selected for staining of the TMA. For 7 of these markers, strength of staining of each core on the TMA was formally scored. Vimentin (positive in ccRCC) and CD9 (positive in chRCC) best distinguished ccRCC from chRCC. The combination of vimentin negativity and CD9 positivity was found to distinguish chRCC from ccRCC with a sensitivity of 100.0% and a specificity of 95.2%. Conclusions: Based on gene expression analysis, we identify CD9 and vimentin as candidate markers for distinguishing between ccRCC and chRCC. In difficult cases and particularly when the amount of diagnostic tissue is limited, vimentin and CD9 staining could serve as a useful adjunct in the differential diagnosis of ccRCC and chRCC. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Disease State: Stage of Clear Cell renal cell carcinoma (I - V))
2010-08-20 | GSE17746 | GEO