scholarly journals A novel highly frequent single‑nucleotide polymorphism site of cadherin 23 in clear cell renal cell carcinoma with sarcomatoid differentiation based on whole exome sequencing

2020 ◽  
Vol 44 (2) ◽  
pp. 735-746
Author(s):  
Wenjuan Yu ◽  
Xiaohui Wang ◽  
Yuewei Wang ◽  
Yanxia Jiang ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Single Nucleotide Polymorphism ◽  
Clear Cell ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide Polymorphism Site ◽  
Cell Renal Cell Carcinoma ◽  
Single Nucleotide ◽  
Whole Exome ◽  
Cadherin 23 ◽  
Sarcomatoid Differentiation

scholarly journals Validation of the Correlation Between Single Nucleotide Polymorphism rs307826 in VEGFR3 and Outcome in Metastatic Clear-Cell Renal Cell Carcinoma Patients Treated with Sunitinib

Kidney Cancer ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 139-149
Author(s):  
Benoit Beuselinck ◽  
Thomas Van Brussel ◽  
Annelies Verbiest ◽  
Maxime Vanmechelen ◽  
Gabrielle Couchy ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Single Nucleotide Polymorphism ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Validation Cohort ◽  
Clear Cell ◽  
Nucleotide Polymorphism ◽  
Discovery Cohort ◽  
Cell Renal Cell Carcinoma ◽  
Single Nucleotide

BACKGROUND: Previously, we have shown a correlation between single nucleotide polymorphism (SNP) rs307826 in vascular endothelial growth factor receptor-3 (VEGFR3) and outcome in metastatic clear-cell renal cell carcinoma (m-ccRCC) patients treated with sunitinib. OBJECTIVE: We aimed to validate this finding in an independent patient series. METHODS: m-ccRCC patients receiving sunitinib as first-line targeted therapy were included in a validation cohort. Endpoints were response rate (RR), progression-free survival (PFS) and overall survival (OS). We also updated survival data of our discovery cohort as described previously. RESULTS: Eighty-four patients were included in the validation cohort. rs307826 AG/GG-carriers had a shorter PFS (8 versus 12 months, p = 0.04) and a trend towards a shorter OS (18 versus 27 months, p = 0.22) compared to AA-carriers. In the total series of 168 patients (from the discovery cohort, as described previously, and the validation cohort), rs307826 AG/GG-carriers had a poorer RR (29% versus 53%, p = 0.008), PFS (8 versus 15 months, p = 0.0002) and OS (22 versus 31 months, p = 0.004) compared to AA-carriers. rs307826 was independently associated with PFS and OS on multivariate analysis. CONCLUSION: VEGFR3 rs307826 seems to be associated with outcome on sunitinib in m-ccRCC. Its impact highlights the role of VEGFR3 in ccRCC pathogenesis and as a target of sunitinib.

Results of a phase II study of atezolizumab and bevacizumab in non-clear cell renal cell carcinoma (nccRCC) and clear cell renal cell carcinoma with sarcomatoid differentiation (sccRCC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 548-548 ◽  
Author(s):  
Rana R. McKay ◽  
Bradley Alexander McGregor ◽  
Kathryn Gray ◽  
John A. Steinharter ◽  
Meghara K. Walsh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Clear Cell ◽  
Collecting Duct ◽  
Cell Renal Cell Carcinoma ◽  
Histologic Subtype ◽  
Sarcomatoid Differentiation

548 Background: NccRCC and sccRCC have historically been underrepresented in clinical trials. Even with targeted therapy, most patients have inferior survival compared to clear cell renal cell carcinoma. The combination of atezolizumab and bevacizumab has demonstrated safety and efficacy in ccRCC. In this multicenter, phase II, open-label, single arm trial we evaluate the efficacy of atezolizumab and bevacizumab in patients with nccRCC and sccRCC with >20% sarcomatoid differentiation. Methods: Eligible patients had an ECOG performance status of 0-2 and may have received prior therapy. Prior PD-1/PD-L1 therapy was not allowed. Patients underwent a mandatory baseline biopsy and subsequently received atezolizumab 120 mg and bevacizumab 15 mg/kg intravenously every 3 weeks. Patients remained on therapy until radiographic progression, unacceptable adverse events, or withdrawal. The primary end point was overall response rate (ORR) as determined by RECIST version 1.1. Results: 65 patients were enrolled of whom 52 had ≥1 response assessment and were included in this analysis. 36 patients had nccRCC (papillary n=14, chromophobe n=8, unclassified RCC n=3, collecting duct n=3, translocation n=3, other n=5), and 16 patients had sccRCC. 17 patients received prior systemic therapy, 16 of whom had nccRCC. The ORR was 31% in the overall cohort (Table 1). 10 patients (19%) developed grade 3 treatment-related adverse events (AEs), half of which were immune-related. There were no grade 4-5 AEs. Conclusions: In this study, we show that therapy with atezolizumab and bevacizumab was safe and demonstrated anti-tumor activity in nccRCC and sccRCC. Further analyses will report ORR by histologic subtype and PD-L1 expression status. Analysis of tissue and blood-based biomarkers of response are ongoing. Clinical trial information: NCT02724878. [Table: see text]

RESEARCH ON PARAMETERIZED ALGORITHMS OF THE INDIVIDUAL HAPLOTYPING PROBLEM

2007 ◽  
Vol 05 (03) ◽  
pp. 795-816 ◽  
Author(s):  
MINZHU XIE ◽  
JIAN'ER CHEN ◽  
JIANXIN WANG
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Time Complexity ◽  
Maximum Length ◽  
Parameterized Algorithms ◽  
Sequencing Data ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide Polymorphism Site ◽  
Single Nucleotide ◽  
The Individual

The individual haplotyping problem is a computing problem of reconstructing two haplotypes for an individual based on several optimal criteria from one's fragments sequencing data. This paper is based on the fact that the length of a fragment and the number of the fragments covering a SNP (single nucleotide polymorphism) site are both very small compared with the length of a sequenced region and the total number of the fragments and introduces the parameterized haplotyping problems. With m fragments whose maximum length is k1, n SNP sites and the number of the fragments covering a SNP site no more than k2, our algorithms can solve the gapless MSR (Minimum SNP Removal) and MFR (Minimum Fragment Removal) problems in the time complexity O(nk1k2 + m log m + nk2 + mk1) and [Formula: see text] respectively. Since, the value of k1 and k2 are both small (about 10) in practice, our algorithms are more efficient and applicable compared with the algorithms of V. Bafna et al. of time complexity O(mn2) and O(m2n + m3), respectively.

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