Comparison of tumor mutational burden (TMB) in PBRM1/BAP1-based subsets of advanced renal cell carcinoma (aRCC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 634-634
Author(s):  
Sumanta K. Pal ◽  
Russell Madison ◽  
Jon Chung ◽  
Neeraj Agarwal ◽  
Paulo Gustavo Bergerot ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Genomic Profiling ◽  
Coverage Depth ◽  
Mutational Burden ◽  
Comprehensive Genomic Profiling ◽  
Tumor Mutational Burden ◽  
Clear Cell Rcc

634 Background: Using IHC, Joseph et al (J Urol 2016) propose that 40.1%, 48.6%, 8.7% and 1.8% of patients (pts) can be characterized as PBRM1+BAP1+, PRBM1-BAP1+, PBRM1+BAP1- and PBRM1-BAP1-, respectively. We sought to confirm consistency of the frequency of genomic alterations (GAs) and IHC data and to compare TMB across subsets. Methods: DNA was extracted from 40 microns of FFPE sections from pts with aRCC. Comprehensive genomic profiling (CGP) was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 688X for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. TMB was determined on 1.2 million Mb of sequenced DNA; results are reported in subsets segregated by presence or absence of PBRM1 and BAP1 alteration. Results: 648 consecutive pts (459:189 M:F) with clear cell RCC (ccRCC) were assessed with a median age of 58, and 368 consecutive pts (254:114 M:F) with non-clear cell RCC (nccRCC) were assessed with a median age of 57. Mutations in BAP1 and PBRM1 were found more frequently in ccRCC vs nccRCC (P < 0.05 for both). In pts with ccRCC, average TMB was highest in pts with co-occurring PBRM1 and BAP1 GAs (4.87 muts/Mb), and lowest in pts lacking both GAs (2.77 muts/Mb) (P < 0.05). TMB was similar across PBRM1/BAP1-based subsets amongst pts with nccRCC. Conclusions: As anticipated, the frequency of PBRM1/BAP1-mutated subsets by CGP is inversely related to the frequency of subsets with PBRM1/BAP1 loss by IHC from previous reports. In addition to these confirmatory findings, this large series identifies that pts with dual PBRM1/ BAP1 GAs (associated with the worst prognosis) had the highest TMB. [Table: see text]

Comprehensive genomic profiling of renal cell carcinoma with sarcomatoid dedifferentiation to pinpoint recurrent genomic alterations.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 537-537
Author(s):  
Gabriel G. Malouf ◽  
Siraj Mahamed Ali ◽  
Kai Wang ◽  
Sohail Balasubramanian ◽  
Jeffrey S. Ross ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Clinical Care ◽  
Genomic Profiling ◽  
Genomic Features ◽  
Routine Clinical Care ◽  
Comprehensive Genomic Profiling ◽  
Worse Prognosis

537 Background: Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is found in five percent of all renal cell carcinoma (RCC) cases, and has a significantly worse prognosis relative to matched highgrade RCC with only epithelial elements. The genomic features underpinning sRCC are not well understood, and at present, there are no specific or effective therapies for sRCC. Methods: We conducted comprehensive genomic profiling (CGP) on paired epithelial and sarcomatoid areas of 3 sRCC cases. In the course of routine clinical care, CGP was performed on another 23 sRCC harboring diverse epithelial components. CGP was conducted using a hybrid capture next generation DNA sequencing assay(NGS) of 236 cancer-related genes plus 19 genes frequently rearranged in cancer. Results were compared with 56 similarly sequenced cases of clear cell RCC devoid of sarcomatoid component, and with clear cell TCGA. Results: Two of three sRCC cases that underwent CGP of both their epithelial and the sarcomatoid components demonstrated identical mutational profiles, and a third case demonstrated commonly disrupted genes. Of the 23 sRCC, TP53(43%), CDKN2A(30%), VHL(26%) and NF2(22%) were the most frequently altered genes. NF2 mutations were mutually exclusive with TP53 but not with VHL mutations. Conclusions: Two of three sRCC cases that underwent CGP of both their epithelial and the sarcomatoid components demonstrated identical mutational profiles, and a third case demonstrated commonly disrupted genes. Of the 23 sRCC, TP53(43%), CDKN2A(30%), VHL(26%) and NF2(22%) were the most frequently altered genes. NF2 mutations were mutually exclusive with TP53 but not with VHL mutations.

Comprehensive genomic profiling in Chinese patients with clear cell renal cell carcinoma.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e13517-e13517
Author(s):  
Baiye Jin ◽  
Yimin Wang ◽  
Jindan Luo ◽  
Yu Wang ◽  
Shuang Ren ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Chinese Patients ◽  
Genomic Profiling ◽  
Cell Renal Cell Carcinoma ◽  
Comprehensive Genomic Profiling

scholarly journals 690P Comprehensive genomic profiling (CGP) of VHL mutated and VHL wild type clear cell renal cell carcinoma (ccRCC)

2021 ◽  
Vol 32 ◽  
pp. S706-S707
Author(s):  
G. Bratslavsky ◽  
P. Grivas ◽  
P.E. Spiess ◽  
B. Decker ◽  
N.A. Danziger ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Genomic Profiling ◽  
Wild Type ◽  
Cell Renal Cell Carcinoma ◽  
Comprehensive Genomic Profiling

scholarly journals Two Cases of Sporadic Eosinophilic Solid and Cystic Renal Cell Carcinoma in Manitoba Population

2021 ◽  
pp. 106689692199322
Author(s):  
Seyed Mohammad Mohaghegh Poor ◽  
Shivani Mathur ◽  
Karl Kassier ◽  
Janetta Rossouw ◽  
Robert Wightman ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Preoperative Imaging ◽  
Renal Neoplasm ◽  
Renal Masses ◽  
Cystic Renal Cell Carcinoma ◽  
Eosinophilic Cytoplasm ◽  
Clear Cell Rcc

Two sporadic cases of eosinophilic solid and cystic renal cell carcinoma (ESC RCC), at our institution, are presented in this study to contribute to the growing literature on this novel renal neoplasm. The first patient was a 38-year-old female with two synchronous renal masses measuring 3.5 and 1.9 cm on preoperative imaging. The second patient was a 44-year-old female with an incidental renal mass measuring 4 cm. Both patients underwent uncomplicated radical nephrectomies. The 1.9 cm mass in the first patient was consistent with clear cell RCC. The dominant mass in the first patient and the tumor in the second patient had microscopic and macroscopic findings in keeping with ESC RCC including a tan appearance, abundant eosinophilic cytoplasm, and CK20+ and CK7− staining. Both patients had an uncomplicated course following surgery with no evidence of local recurrence or distant metastatic disease for 1 and 2 years for the first and second patient accordingly. These cases contribute to a growing body of literature regarding ESC RCC including, to our knowledge, the first reported case of synchronous ESC RCC and clear cell RCC. Further research about this novel renal neoplasm is needed.

scholarly journals Detection of a peritumoral pseudocapsule in patients with renal cell carcinoma undergoing robot-assisted partial nephrectomy using enhanced MDCT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Makoto Toguchi ◽  
Toshio Takagi ◽  
Yuko Ogawa ◽  
Satoru Morita ◽  
Kazuhiko Yoshida ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Partial Nephrectomy ◽  
Renal Cell ◽  
Clear Cell ◽  
Robot Assisted ◽  
High Attenuation ◽  
Papillary Rcc ◽  
Clear Cell Rcc

AbstractTo investigate the detection of peritumoral pseudocapsule (PC) using multi-detector row computed tomography (MDCT) for tumors resected by robot-assisted laparoscopic partial nephrectomy (RAPN) for T1 renal cell carcinoma (RCC). Study participants included 206 patients with clinical T1 RCC who underwent RAPN between October 2017 and February 2018. Two radiologists who were blinded to the pathological findings evaluated the computed tomography (CT) images. Radiological diagnosis of a PC was defined by a combination of observations, including a low-attenuation rim between the tumor and renal cortex in the cortico-medullary phase and a high-attenuation rim at the edge of the tumor in the nephrogenic or excretory phase. A PC was detected on CT in 156/206 tumors (76%) and identified by pathology in 182/206 (88%) tumors including 153/166 (92%) clear cell RCC, 13/14 (93%) papillary RCC, and 7/16 (44%) chromophobe RCC. In the whole cohort, CT findings showed a sensitivity of 81.3% (148/182), specificity of 66.7% (16/24), and positive predictive value of 94.9% (148/156). When the data were stratified according to pathological subtypes, MDCT was observed to have a sensitivity of 86.9% (133/153) and specificity of 61.5% (8/13) in clear cell RCC, sensitivity of 38.5% (5/13) and specificity of 100% (1/1) in papillary RCC, and sensitivity of 44.4% (4/7) and specificity of 66.7% (6/9) in chromophobe RCC. A low or high-attenuation rim around the tumor in the cortico-medullary or nephrographic-to-excretory phase indicates a PC of RCC, though the accuracy is not satisfactory even with 64- or 320-detector MDCT.

scholarly journals Tumor mutational burden and immune infiltrates in renal cell carcinoma and matched brain metastases

ESMO Open ◽  
2021 ◽  
Vol 6 (2) ◽  
pp. 100057
Author(s):  
A. Steindl ◽  
D. Alpar ◽  
G. Heller ◽  
M.J. Mair ◽  
B. Gatterbauer ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Mutational Burden ◽  
Tumor Mutational Burden

Characterization of Clinical Cases of Advanced Papillary Renal Cell Carcinoma via Comprehensive Genomic Profiling

2018 ◽  
Vol 73 (1) ◽  
pp. 71-78 ◽  
Author(s):  
Sumanta K. Pal ◽  
Siraj M. Ali ◽  
Evgeny Yakirevich ◽  
Daniel M. Geynisman ◽  
Jose A. Karam ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Papillary Renal Cell Carcinoma ◽  
Genomic Profiling ◽  
Comprehensive Genomic Profiling ◽  
Clinical Cases

scholarly journals Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor mutational burden, and beyond

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Jason Zhu ◽  
Andrew J. Armstrong ◽  
Terence W. Friedlander ◽  
Won Kim ◽  
Sumanta K. Pal ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Mutational Burden ◽  
Tumor Mutational Burden

Chromophobe Renal Cell Carcinoma With Retrograde Venous Invasion and Gain of Chromosome 21: Potential Harbingers of Aggressive Clinical Behavior

2018 ◽  
Vol 26 (6) ◽  
pp. 536-541 ◽  
Author(s):  
Mohsin Jamal ◽  
Kanika Taneja ◽  
Sohrab Arora ◽  
Ravi Barod ◽  
Craig G. Rogers ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Aggressive Behavior ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Renal Vein ◽  
Clear Cell ◽  
Venous Invasion ◽  
Chromosome 21 ◽  
Chromophobe Rcc ◽  
Clear Cell Rcc

Occasionally, renal cell carcinoma (RCC) with renal vein extension spreads against the flow of blood within vein branches into the kidney, forming multifocal nodules throughout the renal parenchyma. These foci are not regarded as multiple tumors but rather reverse spread of tumor along the venous system. This intravascular spread has previously been reported in clear cell RCC and RCC unclassified. However, to our knowledge, this has never been reported in chromophobe RCC. Chromophobe RCC is a unique histologic subtype of renal cancer, generally thought to have less aggressive behavior. However, it nonetheless has the potential to undergo sarcomatoid dedifferentiation, which is associated with poor prognosis. We report a unique case of a 65-year-old man with chromophobe RCC (pT3a) showing classic morphology (nonsarcomatoid), yet presenting with retrograde venous invasion and hilar lymph node metastasis at the time of right radical nephrectomy. Fluorescence in situ hybridization revealed gain of chromosome 21 with loss of multiple other chromosomes. Partial hepatectomy was performed to resect metastatic RCC 7 months after nephrectomy, revealing chromophobe RCC with classic morphology. Bone biopsy confirmed skeletal metastases 38 months after initial diagnosis. Although invasion of the renal vein and retrograde venous invasion are characteristically seen in clear cell RCC, this unusual phenomenon may also occur in chromophobe RCC, despite its unique tumor biology. This and gain of chromosome 21, which was postulated to be associated with aggressive behavior in a previous report, were associated with adverse behavior in our patient, who had short-term progression to multi-organ metastatic disease.

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