scholarly journals Cell-free Circulating Tumor DNA (ctDNA) in Metastatic Renal Cell Carcinoma (mRCC): Current Knowledge and Potential Uses

Kidney Cancer ◽  
2019 ◽  
Vol 3 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Andrew W. Hahn ◽  
Roberto H. Nussenzveig ◽  
Benjamin L. Maughan ◽  
Neeraj Agarwal
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Current Knowledge ◽  
Circulating Tumor Dna ◽  
Tumor Dna

Plasma Circulating Tumor DNA and Clonal Hematopoiesis in Metastatic Renal Cell Carcinoma

2020 ◽  
Vol 18 (4) ◽  
pp. 322-331.e2 ◽  
Author(s):  
Jack V.W. Bacon ◽  
Matti Annala ◽  
Maryam Soleimani ◽  
Jean-Michel Lavoie ◽  
Alan So ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Circulating Tumor Dna ◽  
Clonal Hematopoiesis ◽  
Tumor Dna

Circulating tumor DNA sequencing analysis of patients with metastatic renal cell carcinoma (mRCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17100-e17100
Author(s):  
Zeynep Busra Zengin ◽  
Nazli Dizman ◽  
Nicholas Salgia ◽  
Jeremy Jones ◽  
Jingbo Zhang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Circulating Tumor Dna ◽  
Response To Therapy ◽  
Sequencing Analysis ◽  
Invasive Approach ◽  
Treatment Type ◽  
Tumor Dna

e17100 Background: Despite extensive work to characterize genomic alterations (GAs) in metastatic renal cell carcinoma (mRCC), GAs are not currently used for treatment sequencing or selection. Circulating tumor DNA (ctDNA) in both blood and urine may elucidate potential mRCC biomarkers through a minimally invasive approach. We aimed to validate previous blood-based ctDNA studies (Pal et al Eur Urol 2017) and compare detection rates of clinically relevant GAs in plasma and urine. Methods: From a single institution, patients (pts) with mRCC were recruited to provide a plasma and urine specimen. ctDNA next-generation sequencing was performed using an investigational 120-gene panel, and we limited our assessment to 7 GAs with biological relevance in RCC ( VHL, MTOR, PIK3CA, TSC2, MET, AKT1, TSC1). Further, only pathogenic alterations previously recognized in RCC and cited in the Catalogue of Somatic Mutations in Cancer (COSMIC) database were considered. Clinicopathologic variables, treatment type and response to therapy were collected from an institutional mRCC patient database. Concordance analysis was performed at the gene level between blood and urine using previously published approaches (Chae et al Oncotarget 2016). Results: 50 pts (40M:10F) were enrolled with a median age of 65. 40 pts (80%) had clear cell histology, while the remainder were papillary (12%), chromophobe (4%) or other (4%). Pts received a median of 1 line of therapy (range, 0-7). GAs were identified in 45 pts (90%) in blood and in 45 pts (90%) in urine . Applying the above criteria, the most frequently observed GAs in blood specimens were TSC2 (9%), MTOR (4%), and VHL (2%). The most frequently observed GAs in urine were VHL (4%) and MTOR (2%). The rate of concordance between blood- and urine-detected GAs was 93%. Of pts bearing mTOR pathway alterations in blood or urine, 3 received everolimus-based therapy. All 3 pts remain on therapy at 10.4, 13.8 and 14.0 months, respectively. Conclusions: Biologically relevant GAs can be detected in pts with mRCC using blood and urine. Our methodology showed high concordance between both platforms. Consistent with prior reports, ctDNA assessment of pts with pretreated mRCC shows a higher frequency of TOR pathway alterations and a lower frequency of VHL mutation.

scholarly journals Circulating tumor DNA analysis of metastatic renal cell carcinoma

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Jingbo Zhang ◽  
Yunchao Liu ◽  
Bing Xu ◽  
Fuwei Li ◽  
Yan Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Dna Analysis ◽  
Circulating Tumor Dna ◽  
Tumor Dna

scholarly journals Association of Circulating Tumor DNA (ctDNA) Detection in Metastatic Renal Cell Carcinoma (mRCC) with Tumor Burden

Kidney Cancer ◽  
2017 ◽  
Vol 1 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Manuel Caitano Maia ◽  
Paulo Gustavo Bergerot ◽  
Nazli Dizman ◽  
JoAnn Hsu ◽  
Jeremy Jones ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Tumor Dna

Evolution of Circulating Tumor DNA Profile from First-line to Subsequent Therapy in Metastatic Renal Cell Carcinoma

2017 ◽  
Vol 72 (4) ◽  
pp. 557-564 ◽  
Author(s):  
Sumanta K. Pal ◽  
Guru Sonpavde ◽  
Neeraj Agarwal ◽  
Nicholas J. Vogelzang ◽  
Sandy Srinivas ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Circulating Tumor Dna ◽  
First Line ◽  
Dna Profile ◽  
Tumor Dna

Complementary role of circulating tumor DNA assessment and tissue genomic profiling in metastatic renal cell carcinoma

2021 ◽  
pp. clincanres.0572.2021
Author(s):  
Zeynep B. Zengin ◽  
Caroline Weipert ◽  
Nicholas J. Salgia ◽  
Nazli Dizman ◽  
Joann Hsu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Circulating Tumor Dna ◽  
Genomic Profiling ◽  
Complementary Role ◽  
Tumor Dna

scholarly journals Clinical significance of the mutational landscape and fragmentation of circulating tumor DNA in renal cell carcinoma

2019 ◽  
Vol 110 (2) ◽  
pp. 617-628 ◽  
Author(s):  
Yoshiyuki Yamamoto ◽  
Motohide Uemura ◽  
Masashi Fujita ◽  
Kazuhiro Maejima ◽  
Yoko Koh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Significance ◽  
Renal Cell ◽  
Circulating Tumor Dna ◽  
Mutational Landscape ◽  
Tumor Dna

Detection of circulating tumor DNA in patients with metastatic clear cell renal cell carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16105-e16105 ◽  
Author(s):  
Lucia Nappi ◽  
Jack Bacon ◽  
Matti Annala ◽  
Maryam Soleimani ◽  
Jean-Michel Lavoie ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Predictive Biomarkers ◽  
Germline Mutations ◽  
Circulating Tumor Dna ◽  
Ffpe Tissue ◽  
Cell Renal Cell Carcinoma ◽  
Tumor Dna

e16105 Background: Clear cell renal cell carcinoma (ccRCC) represents the most common presentation of kidney cancer. Patient outcomes have significantly improved with the approval of several targeted agents over the past decade. However, the lack of predictive biomarkers has hampered treatment optimization. Circulating tumor DNA (ctDNA) has emerged as an effective, minimally-invasive alternative to tissue for profiling the tumor genome in other tumors. Methods: Blood samples were collected from patients (pts) with metastatic ccRCC for next-generation sequencing of cell free DNA and germline DNA. Targeted sequencing was performed using the Roche Human Oncology Design panel of 981 genes to a median depth of 937x unique reads. Matched FFPE tissue was available from 14 pts and profiled using the same assay. Results: Samples from 52 metastatic, treatment-naïve pts were analyzed. Germline mutations were detected in 6/52 (11%) of the pts with the most frequent abnormalities affecting ATM, PALB2, RAD51D, CHEK2, BRCA1. Median ctDNA fraction was 3.9% (2-40%) with a median of 2 mutations/pt. Somatic mutations were detected in 29/52 (56%) of the samples; of those, 15/29 (51%) of pts harbored RCC-related genes mutations, 3/29 (10%) non-coding mutations and 10/29 (34%) alterations in non RCC-associated genes. Median variant allele frequency was 1.9% (1-22%). Consistent with tissue-based reports, VHL, BAP1, PBRM1, and TP53 were the most frequently altered genes. Lastly, 50% of the patient-matched FFPE tissue samples shared a fully concordant mutation profile. Conclusions: We confirmed a high prevalence of germline mutations in pts with ccRCC. The rate of ctDNA detection in metastatic ccRCC appears to be lower than in other metastatic solid tumors. Furthermore, it is not yet clear whether all the detected somatic alterations are strictly ccRCC-ctDNA dependent. Nevertheless, a quarter of pts exhibited clinically-informative ccRCC associated alterations in their liquid biopsy. These findings suggest that ctDNA is a promising tool for genomic profiling in a subset of patients with metastatic ccRCC.

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