scholarly journals Whole-genome and transcriptome profiling of a metastatic thyroid-like follicular renal cell carcinoma

2018 ◽  
Vol 4 (6) ◽  
pp. a003137 ◽  
Author(s):  
Jenny J. Ko ◽  
Jasleen K. Grewal ◽  
Tony Ng ◽  
Jean-Michel Lavoie ◽  
My Linh Thibodeau ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Transcriptome Profiling ◽  
Whole Genome

Multilevel Whole-Genome Analysis Reveals Candidate Biomarkers in Clear Cell Renal Cell Carcinoma

2012 ◽  
Vol 72 (20) ◽  
pp. 5273-5284 ◽  
Author(s):  
Andrew H. Girgis ◽  
Vladimir V. Iakovlev ◽  
Ben Beheshti ◽  
Jane Bayani ◽  
Jeremy A. Squire ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Genome Analysis ◽  
Renal Cell ◽  
Clear Cell ◽  
Whole Genome ◽  
Cell Renal Cell Carcinoma ◽  
Whole Genome Analysis

Understanding the genomic underpinnings of metastatic chromophobe renal cell carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 513-513 ◽  
Author(s):  
Jozefina Casuscelli ◽  
Patricia Wang ◽  
Almedina Redzematovic ◽  
William Lee ◽  
Venkatraman E. Seshan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Renal Cell ◽  
Chromophobe Renal Cell Carcinoma ◽  
Whole Genome ◽  
Next Generation ◽  
Metastatic Tumors ◽  
Histologic Subtype

513 Background: Chromophobe renal cell carcinoma (chRCC) is the third most common histologic subtype of kidney cancer. While most of these tumors have an indolent behavior, 7% of patients with chRCC develop metastases, with no currently available standard of care. The Cancer Genome Atlas characterized chRCC, highlighting pathognomonic single copy chromosomal losses of 1, 2, 6, 10, 13 and 17, as well as a minimal mutation burden distinguishing it from all other cancer types. However, only 15% of the analyzed patients had advanced disease. We analyzed metastatic chRCC to further characterize these tumors and elucidate mechanisms leading to aggressive disease using a variety of next generation and whole genome sequencing. Methods: Our cohort of metastatic chRCC consisted of 40 patients with available clinical and pathologic data. Whole genome sequencing (WGS) was performed on 6 patients (4 primary tumors and 2 metastases), 42 additional samples from 33 patients were analyzed using targeted next-generation sequencing (MSK-IMPACT). Notably, we were able to collect and analyze matched primary and metastatic tumors from 7 patients. As control cohort 27 non-metastatic chRCC tumors were sequenced with MSK-IMPACT. Copy number patterns were computed with OncoSNP seq and FACETS. Results: The most commonly mutated genes in the aggressive chRCC tumors were TP53 and PTEN (WGS: TP53 67 %, PTEN 33%; MSK-IMPACT: TP53 61%, PTEN 27%). No other genes were mutated frequently. Primary tumor samples of chRCC did show the typical pattern of chromosomal losses in 1, 2, 6, 10, 13 and 17. Interestingly, these canonical losses could not be detected in the metastases even when accounting for tumor purity. Conclusions: TP53 and PTEN mutations are highly enriched in both primary and metastatic tumors of aggressive chRCC compared to the non-aggressive tumors and likely play a critical role in disease progression. More intriguingly, the observation of differential copy numbers in matched primary and metastatic tumors suggest whole genome or whole chromosome events in these samples. We are currently employing different bioinformatic and cytogenetic platforms to validate our novel hypothesis of chromosomal events as driver for metastatic development in chRCC.

Abstract 4719: Novel germline variants in hereditary renal cell carcinoma genes elucidated by whole genome sequencing

2020 ◽  
Author(s):  
Cathy D. Vocke ◽  
Christopher J. Ricketts ◽  
Daniel R. Crooks ◽  
Martin Lang ◽  
Laura S. Schmidt ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Renal Cell ◽  
Whole Genome ◽  
Germline Variants

scholarly journals Cryptic Promoter Activation Drives POU5F1 (OCT4) Expression in Renal Cell Carcinoma

2018 ◽  
Author(s):  
Kyle T. Siebenthall ◽  
Chris P. Miller ◽  
Jeff D. Vierstra ◽  
Julie Mathieu ◽  
Maria Tretiakova ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Transcriptome Profiling ◽  
Advanced Tumor Stage ◽  
Cryptic Promoter ◽  
Advanced Tumor ◽  
Hif Pathway

Transcriptional dysregulation drives cancer formation but the underlying mechanisms are still poorly understood. As a model system, we used renal cell carcinoma (RCC), the most common malignant kidney tumor which canonically activates the hypoxia-inducible transcription factor (HIF) pathway. We performed genome-wide chromatin accessibility and transcriptome profiling on paired tumor/normal samples and found that numerous transcription factors with a RCC-selective expression pattern also demonstrated evidence of HIF binding in the vicinity of their gene body. Some of these transcription factors influenced the tumor’s regulatory landscape, notably the stem cell transcription factor POU5F1 (OCT4). Unexpectedly, we discovered a HIF-pathway-responsive cryptic promoter embedded within a human-specific retroviral repeat element that drives POU5F1 expression in RCC via a novel transcript. Elevat POU5F1 expression levels were correlated with advanced tumor stage and poorer overall survival in RCC patients. Thus, integrated transcriptomic and epigenomic analysis of even a small number of primary patient samples revealed remarkably convergent shared regulatory landscapes and a novel mechanism for dysregulated expression of POU5F1 in RCC.

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