CHEK2 mutation in renal cell carcinoma (RCC): Single center experience.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 480-480
Author(s):  
Joanna Huszno ◽  
Magdalena Mazur ◽  
Elzbieta Nowara ◽  
Ewa Grzybowska
Keyword(s):  
Breast Cancer ◽  
Renal Cell Carcinoma ◽  
Family History ◽  
Cell Carcinoma ◽  
Renal Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Chek2 Mutation ◽  
Mutation Carriers ◽  
Cell Renal Cancer

480 Background: Renal cell cancer (RCC) accounts for about 4% of all the adult malignancies. RCC occurs in both sporadic and heritable forms. Genetic mutations have been identified as the cause of inherited cancer risk in 1% to 2% of RCC cases overall. In some studies, variant I157T of CHEK2 gene were found to be associated with increased risk of clear cell renal cancer. The aim of this study was to evaluate the association between CHEK2 mutation and RCC in our centre. Methods: We reviewed the medical records of 43 clear cell renal cancer patients (pts) who were diagnosed and treated in COI in Gliwice. Mutation profile was assessed by RFLP-PCR technique. In Poland, there are three polymorphic variants of CHEK2 1100delC, IVS2+1G →A (premature protein truncation), and a common missense variant (I157T) (substitution of an isoleucine for a threonine). We evaluated the presence of CHEK2 mutation in clear cell carcinoma. Results: In our study CHEK2 mutation (variant I157T) was detected in 7% pts. The median age of pts was 57 years (range from 34 to 74). Most of the patients were women (87%). All CHEK2 mutation carriers were women and were >65 years old. Cancer in family history were reported in 80% pts. Most frequently were: breast cancer (33%), gynecological cancers (33%), gastrointestinal cancers (27%), and renal cell carcinoma (20%). There was also described lung cancer in family history (7%). The most frequent cancers in family history in CHEK2 mutation carriers were: breast cancer and gynecological cancers. 20% of pts had other cancers in their history (breast cancer, ovarian cancer, and contralateral renal cell carcinoma). Contralateral renal cell carcinoma was reported in CHEK2 mutation carrier. All pts had nephrectomy due to RCC and all had clear cell renal cancer in histopathologic examination. All CHEK2 mutation carriers had higher grade (grade 3) and capsular invasion. 5% of CHEK2 mutation carriers had TP53 (c.[215G>C])polymorphism. Conclusions: Variant I157T of CHEK2 gene were found to be associated with increased risk of cancer in family history (breast cancer, gynecological cancer), and renal cancer of contralateral kidney. Factors associated with CHEK2 mutation carriers were higher histologic grade (G3) and elderly age.

scholarly journals Characterization of the breast cancer resistance protein (BCRP/ABCG2 ) in clear cell renal cell carcinoma

2018 ◽  
Vol 143 (12) ◽  
pp. 3181-3193 ◽  
Author(s):  
Anna Reustle ◽  
Pascale Fisel ◽  
Olga Renner ◽  
Florian Büttner ◽  
Stefan Winter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Breast Cancer Resistance Protein ◽  
Clear Cell ◽  
Cancer Resistance ◽  
Cell Renal Cell Carcinoma ◽  
Resistance Protein

The impact of family history on pathological and clinical outcomes in non-syndromic clear cell renal cell carcinoma

2010 ◽  
Vol 106 (11) ◽  
pp. 1638-1642 ◽  
Author(s):  
Matthew K. Tollefson ◽  
Stephen A. Boorjian ◽  
Christine M. Lohse ◽  
Michael L. Blute ◽  
Bradley C. Leibovich
Keyword(s):  
Renal Cell Carcinoma ◽  
Family History ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
The Impact

scholarly journals Studying the Association Between Breast Cancer and Renal Cell Carcinoma

2021 ◽  
Author(s):  
Khalid A Jazieh ◽  
Firas Baidoun ◽  
Nataly Torrejon ◽  
Zahi Merjaneh ◽  
Anas Saad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Renal Cell Carcinoma ◽  
Genetic Testing ◽  
Family History ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Case Reports ◽  
Population Data ◽  
Seer Database ◽  
History Of

Abstract Purpose: There are case reports of patients with both primary breast cancer (BC) and renal cell carcinoma (RCC). We explore the association between these two malignancies using SEER population data and our institutional records.Methods: We studied the association between BC and RCC in the 2000-2016 Surveillance, Epidemiology and End Results (SEER) database. We then reviewed our hospital records of patients with both BC and RCC and collected information including personal and family history of cancers, genetic testing, and patient outcomes.Results: Of the 813,477 females diagnosed with BC in the SEER database, 1,914 later developed RCC. The risk of developing RCC was significantly increased within the first six months, 7-12 months, and 1-5 years following BC diagnosis with standardized incidence ratios (SIRs) of 5.08 (95% CI, 4.62- 5.57), 2.09 (95% CI, 1.8-2.42), and 1.15 (95% CI, 1.06-1.24), respectively. Of 56,200 females with RCC, 1,087 later developed BC. The risk of developing BC following RCC was elevated within the first six months (SIR of 1.45 [95% CI, 1.20-1.73]). For our hospital patients, 437 had both BC and RCC. 427 (97.71%) were female, and 358 (81.92%) were white, and breast cancer was diagnosed before RCC in 246 (61.5%) patients. There were 15 germline mutations in those with genetic testing. Conclusion:Our findings suggest that BC patients are at higher risk of developing RCC and vice versa. BC tended to precede RCC, and patients frequently had personal histories of other malignancies and a family history of cancer, particularly BC.

Robustness of the 16-gene signature for prediction of recurrence-free interval in localized clear cell renal cell carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 455-455
Author(s):  
Bernard J. Escudier ◽  
Serge Koscielny ◽  
Tara Maddala ◽  
Christer Svedman ◽  
Virginie Verkarre ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Gene Signature ◽  
Stage I ◽  
Rt Pcr ◽  
Cell Renal Cell Carcinoma ◽  
Risk Of Recurrence

455 Background: The Renal Cancer assay is a clinically validated RT-PCR assay developed to estimate the risk of recurrence in stage I-III clear cell renal cell carcinoma (ccRCC) patients (pts) treated with nephrectomy. The assay measures expression of 16 genes that are combined to calculate the Recurrence Score result (RS). The RS is associated with recurrence, renal cancer-specific survival and overall survival (all p<0.001) (Escudier, ASCO 2014). The performance of the RS in clinically relevant subgroups, compared to the Leibovich score, and its within-patient variability was examined. Methods: The algorithm, endpoints, methods, and analysis plan were pre-specified prior to merging clinical and molecular data. RT-PCR of RNA from fixed paraffin-embedded ccRCC tissue was performed without knowledge of clinical data. Recurrence-free internval (RFI) was analyzed using Cox regression stratified by stage with data censored at 5 years, and Kaplan-Meier methods. Multivariable models incorporating the Leibovich score were used to assess the additional contribution of the RS to prediction of recurrence. Within- and between-tumor block reproducibility was assessed in an independent study using two separate tumor blocks from 8 pts, where each block was analyzed at 3 depths. Results: RS was generated in 626/645 pts (97%): 398 stage I, 54 stage II, 174 stage III. Median follow up was 5.5 yrs. The RS was significantly associated with risk of recurrence after adjustment for the Leibovich score (HR=4.20, p<0.001). Additionally, the performance of RS was similar across age groups (<60, 60-70 or ≥70), gender, nephrectomy type, tumor size (≤4, 4-7 or >7cm), grade, and presence/absence of invasion (all interaction p>0.29). Within-patient variability in the score (std. dev. of 1.73 and 4.74 RS units for within- and between-tumor block, respectively) was lower than patient-to-patient variability (std. dev. of 15.6 in validation study). Conclusions: The 16-gene signature remains strongly associated with risk of recurrence after adjustment for the Leibovich score and performs consistently across clinically relevant subgroups. Examination of within-patient and between-patient variability indicates that the score is robust to tumor heterogeneity.

scholarly journals Porcupine Inhibitor LGK974 Downregulates the Wnt Signaling Pathway and Inhibits Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Jianyi Li ◽  
Guangzhen Wu ◽  
Yingkun Xu ◽  
Jiatong Li ◽  
Ningke Ruan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Wnt Signaling ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Wnt Signaling Pathway ◽  
Cell Renal Cell Carcinoma ◽  
Wnt Proteins

Targeted therapy for kidney cancer has achieved significant clinical results. However, because most patients who use targeted therapy will develop drug resistance, we still need to constantly explore new therapeutic targets. Although porcupine (PORCN) as a palmitoyltransferase plays a crucial role in the activation and secretion of Wnt proteins and affects the activity of the Wnt signaling pathway, little is known about the role of PORCN in clear cell renal cell carcinoma (ccRCC). We found that PORCN is highly expressed in renal cancer cell lines and patients with renal cell carcinoma with high expression of PORCN have a poor prognosis. Pathway analysis of PORCN and its related proteins showed that PORCN played a role through the Wnt signaling pathway, and there was a strong coexpression relationship between PORCN and Wnt proteins. Therefore, PORCN may be a potential and effective target for ccRCC. In the present study, we found that LGK974 could inhibit proliferation and colony formation and induce apoptosis in ccRCC cells. We also found that LGK974 could inhibit the migration and invasion of renal cell carcinoma and reduce the expression of mesenchymal markers. After treatment with LGK974, the expression level of β-catenin, a key protein in the classical Wnt pathway, was significantly decreased, and the expression levels of the target genes cyclin D1, c-Myc, MMP9, and MMP2 in the Wnt signaling pathway were also significantly decreased, which represented a significant decrease in the activity of the Wnt signaling pathway. At the same time, the cycle of renal cancer cells was significantly blocked. In conclusion, our results indicate that LGK974 could significantly inhibit the progression of renal cancer cells in a safe concentration range, so PORCN may be a safe and effective target for patients with renal cancer.

scholarly journals mTORC2 mediate FLCN-induced HIF2α nuclear import and proliferation of clear cell renal cell carcinoma

2020 ◽  
Author(s):  
Xuyang Zhao ◽  
Yadong Ma ◽  
Jie Cui ◽  
Haiyang Zhao ◽  
Lei Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Molecular Mechanism ◽  
Renal Cancer ◽  
Cancer Progression ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Invasion And Migration ◽  
And Migration

AbstractClear cell renal cell carcinoma (ccRCC), as the most important type of renal carcinoma, has a high incidence and easy metastasis. Folliculin (FLCN) was identified as a tumor suppressor gene. Its deletions and mutations are associated with a potential risk of kidney cancer. At present, the specific molecular mechanism of FLCN-induced proliferation, invasion and migration in clear cell renal cell carcinoma remains elusive.In this study, we demonstrated that FLCN controled cell proliferation, invasion and migration through PI3K/mTORC2 pathway. FLCN combined with HIF2α in various normal and cancerous renal cells, and mTORC2 mediate FLCN effectively alleviated the deterioration of renal cancer cells by degrading HIF2α. Silencing of FLCN showed promotion of HIF2α protein expression, which in turn led to an increase in downstream target genes Cyclin D1 and MMP9. Moreover, when interfering with siFLCN, HIF2α degradation rate was delayed, and the time of entry into the nucleus was advanced. Taken together, our study illustrated that mTORC2 promoted the specific molecular mechanism of HIF2α by down-regulated FLCN, and might be a new therapeutic target against renal cancer progression.

Medicines use review in renal cancer: How are we doing? What could we do better?

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 458-458 ◽  
Author(s):  
Nicholas James MacLeod
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Performance Status ◽  
Electronic Prescribing ◽  
Expanded Access ◽  
Medicines Use ◽  
Medicines Use Review

458 Background: Following guidance from the National Institute for Clinical Excellence (NICE), sunitinib became available for use in the West of Scotland (WOS) in March 2009 as first line treatment for patients with advanced renal cell carcinoma (RCC) who were suitable for immunotherapy and had a performance status (PS) of 0 or 1. We performed a Medicines Use Review of sunitinib in patients who commenced treatment between March 2009 and February 2010. Data were analysed in April 2011. Methods: Patients were identified from an electronic prescribing database. A mixture of prospective and retrospective data were collected using case notes and electronic patient records. Results: 89 patients commenced treatment during this time. 16 patients were excluded as they were enrolled in clinical trials. 73 patients were included in the study. 54 (74%) were male. At the time of analysis, 31 patients were alive. Mean age at first cycle was 62 years. 22 (30%) patients had non clear cell pathology (NCC). 59 (81%) patients had prior nephrectomy and 31 (42%) had prior drug therapy. Median duration of therapy was 6.9 months. Median survival (MS) was 14.4 months (15.1 months for clear cell patients and 8.1 months for non clear cell patients). The most common toxicities (grade 2 or above) were cutaneous, diarrhoea and fatigue. PS was not documented for 43 patients. Where PS was documented, 13 were PS 0, 13 were PS 1 and 4 were PS 2. 32 patients required at least one dose reduction. Three patients later had their dose re-escalated. Conclusions: Our survival figures are lower than those reported in the pivotal trial 1, but comparable to the expanded access programme 2. This may reflect the high proportion of our patients with NCC and with prior treatment. 1. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cancer. J Clin Oncol 27 (22): 3584-90, 2009. 2. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded access trial. Lan Oncol 10: 757-63, 2009.

scholarly journals GATA3 suppresses human fibroblasts-induced metastasis of clear cell renal cell carcinoma via an anti-IL6/STAT3 mechanism

2019 ◽  
Vol 27 (9) ◽  
pp. 726-738 ◽  
Author(s):  
Qianqian Shi ◽  
Renfang Xu ◽  
Guanglai Song ◽  
Hao Lu ◽  
Dong Xue ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Conditioned Medium ◽  
Renal Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Normal Fibroblast ◽  
Cell Renal Cell Carcinoma ◽  
Renal Cancer Cell

AbstractTumorigenesis and metastasis depend on intricate interactions between genetically altered tumor cells and their surrounding microenvironment. It is, however, unclear regarding the molecular mechanisms underlying the progress and metastasis of human clear-cell renal cell carcinoma in the microenvironment with fibroblasts. In this work, we investigated the effect of normal fibroblasts on the metastasis of renal cancer and the relevant signaling pathways. We isolated normal fibroblasts from normal renal tissues and used normal fibroblast-conditioned medium culture renal cancer cells. The CCK-8 and transwell assays showed that normal fibroblasts conditioned medium significantly enhanced ccRCC cell migration. IL6 mediated the cross talk between normal fibroblasts and the cancer cells, and promoted tumor cell migration through the STAT3 pathway. In contrast, GATA3 was downregulated at both mRNA and protein levels in the normal fibroblast-conditioned medium treated with renal cancer cells, but upregulated in adjacent normal tissues. GATA3 overexpression significantly reduced STAT3 phosphorylation and attenuated the migration in both renal cancer cell and IL6-stimulated renal cancer cell. Taken together, our findings suggest that the IL6/STAT3 pathway plays a crucial role in the normal fibroblast-enhanced clear-cell renal cell carcinoma metastasis, while GATA3 may mitigate this effect by inhibiting IL6/STAT3 signaling.

Multiple Chromophobe and Clear Cell Renal Cancer in A Patient Affected by Birt-Hogg-Dubè Syndrome: A Case Report

2016 ◽  
Vol 84 (2) ◽  
pp. 116-120
Author(s):  
Roberto Castellucci ◽  
Michele Marchioni ◽  
Sergio Valenti ◽  
Giuseppe Sortino ◽  
Giulio Borgonovo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cancer ◽  
Renal Cell ◽  
Spontaneous Pneumothorax ◽  
Clear Cell ◽  
Renal Tumors ◽  
Kidney Tumors ◽  
Pulmonary Cysts

Objectives Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. The syndrome is linked to mutations in the FLCN gene, which is preferentially expressed in the skin, kidney, and lung. The aim of our paper is to describe a case of multiple bilateral renal cancer in a patient affected by BHDS. Case Presentation Patient subjected to enucleoresection seven kidney tumors discovered right after ultrasound performed for other reasons. Definitive histologic examination were as follows: multifocal type chromophobe renal cell carcinoma and clear cell. After 1 month, the patient was readmitted for spontaneous pneumothorax. After about a year, the patient was again subjected to resection of multiple renal tumors left. Histological examination proved that it was multifocal renal cell carcinoma, clear cell varieties. The genome analysis highlighted positive for mutation c. 1379_1380 of FLCN gene, BHDS gene. Currently, the patient is under close follow-up. After 1 year, the chest computed tomography (CT) confirmed the presence of minute air bubbles scattered on both sides. Instead, the abdominal CT was positive for a small round lesion 6 mm exophytic. Conclusions The BHDS is a rare syndrome whose management is extremely complex both in terms of oncological and functional. Kidney tumors associated with BHDS usually have a favorable clinical course. Present evidence suggests a close follow-up of the carriers of the genetic mutation patients whether or not they have expressed the lesions of disease given the high rate of recurrence of renal lesions.

Sign in / Sign up

Export Citation Format

Share Document