Comprehensive Genomic Profiling of Adult Renal Sarcomas Provides Insight into Disease Biology and Opportunities for Targeted Therapies

Yakirevich, Evgeny; Madison, Russell; Fridman, Eduard; Mangray, Shamlal; Carneiro, Benedito A.; Lu, Shaolei; Cooke, Matthew; Bratslavsky, Gennady; Webster, Jennifer; Ross, Jeffrey S.; Ali, Siraj M.

doi:10.1016/j.euo.2019.04.002

Cited by 7 publications

(14 citation statements)

References 33 publications

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“…The vacuoles contain acid mucin rather than neutral fat as in lipoblasts 30 . To the best of our knowledge only three cases of renal MFS have already been reported 4 , 34 , 35 ( Tab. II ).…”

Section: Discussionmentioning

confidence: 99%

“…Although MFS belongs to the subgroup of non-translocation-related sarcomas with higher chromosomal instability, it deserves genomic profiling as it can reveal clinically relevant genomic alterations for tailored treatments 35 .…”

Section: Discussionmentioning

confidence: 99%

“…Yakirevich et al conducted comprehensive genomic profiling (CGP) in 13 adult renal sarcomas including a case of MFS 35 . Their MFS had amplifications of two adjacent receptor tyrosine kinase genes ( KIT and PDGFR ) encoding KIT and PDGFR-α proteins that can be modulated by tyrosine kinase inhibitors such as pazopanib 35 . Olaratumab, a monoclonal antibody against PDGFR-α, can improve overall survival 35 .…”

Section: Discussionmentioning

confidence: 99%

“…Their MFS had amplifications of two adjacent receptor tyrosine kinase genes ( KIT and PDGFR ) encoding KIT and PDGFR-α proteins that can be modulated by tyrosine kinase inhibitors such as pazopanib 35 . Olaratumab, a monoclonal antibody against PDGFR-α, can improve overall survival 35 . The MFS reported by Yakirevich et al had also homozygous deletion of tumor suppressor genes CDKN2A (that encodes p16INKa and p14ARF) and CDKN2B (that encodes p15INK4b) 35 .…”

Section: Discussionmentioning

confidence: 99%

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Report of two primary renal tumors with myxoid features. Differential diagnosis between benign and malignant entities

et al. 2021

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Summary Renal mesenchymal neoplasms are rare entities which can have a benign or a malignant behavior. Herein we describe two renal mesenchymal tumors with myxoid stroma, investigating the wide spectrum of differential diagnosis. With our first case we considered some benign entities such as myxoma, myxoid leiomyoma, and mixed epithelial and stromal tumor; with our second case we considered some sarcomas with myxoid features such as myxofibrosarcoma, low-grade fibromyxoid sarcoma, dedifferentiated liposarcoma, and myxoid liposarcoma. During the diagnostic process, it is important to integrate histopathological, immunohistochemical, and molecular data in order to avoid misdiagnosis. We concluded our second case report was a myxofibrosarcoma grade 1. To the best of our knowledge, we described the fourth primary renal myxofibrosarcoma reported in literature.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Report of two primary renal tumors with myxoid features. Differential diagnosis between benign and malignant entities

et al. 2021

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“…In this context, comprehensive genomic profiling (CGP) analysis can provide significant insights into the biology of several tumors, allowing detection of numerous genomic alterations that could help elucidate the biology and potentially suggest strategies for precision oncology clinical trials [6,7]. In this study, we profiled a group of 296 RPS and analyzed the frequency of genomic alterations (GAs), hypothesizing that we would identify distinct therapeutic opportunities for patients affected by these rare malignancies.…”

Section: Introductionmentioning

confidence: 99%

Primary Adult Retroperitoneal Sarcoma: A Comprehensive Genomic Profiling Study

Necchi¹,

Basile²,

Pederzoli³

et al. 2021

Société Internationale D’Urologie Journal

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Background: Adult primary retroperitoneal sarcomas (RPSs) are a group of heterogeneous tumors with different histological subtypes. Comprehensive genomic profiling (CGP) analyses have recently provided significant insights into the biology of sarcomas by identifying genomic alterations (GAs) which could benefit from targeted therapies. Methods: RPS were evaluated by CGP using next-generation sequencing of up to 406 cancer-related genes. Tumor mutational burden (TMB) was determined on 0.83 to 1.14 mut/Mb of sequenced DNA. Finally, PD-L1 expression was determined. Results: Overall, 296 cases of primary RPS were analyzed. Liposarcoma (LPS) subtype had more GA/tumor than leiomyosarcoma (LMS) subtypes, with follicular dendritic cell sarcomas harboring the highest and synovial sarcomas the lowest. TP53 and Rb1 alterations were the highest in LMS, and CDK4/6 and MDM2 in LPS. However, both the TMB and targetable GA rates were low across subtypes. PD-L1 immunostaining was low positive in 21% and high positive in 5% of patients, respectively. Conclusions: CGP analysis revealed that potentially actionable genomic targets were rare in our cohort of RPS. Moreover, RPSs seem less likely to respond to immune checkpoint inhibitors based on putative biomarkers status. Nevertheless, genomic stratification according to histological subtypes led to description of GAs that can inform future clinical trials design.

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Identifying Opportunities and Challenges for Patients With Sarcoma as a Result of Comprehensive Genomic Profiling of Sarcoma Specimens

Hay

Severson²,

Miller³

et al. 2020

JCO Precision Oncology

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PURPOSE Comprehensive genomic profiling (CGP) of sarcomas is rapidly being integrated into routine clinical care to help refine diagnosis and prognosis and determine treatment. However, little is known about barriers to successful CGP or its clinical utility in sarcoma. We set out to determine whether CGP alters physician treatment decision-making, and whether sarcoma subtypes influence the frequency of successful technical performance of CGP. METHODS A single-institution study evaluated profiling outcomes of 392 samples from patients with sarcoma, using a commercially available CGP panel. Of this group, 34 patients were evaluated prospectively (Decision Impact Trial) to evaluate the utility of CGP in physician decision-making. All cases were retrospectively analyzed to identify causes of CGP failure. RESULTS CGP successfully interrogated 75.3% (n = 295 of 392) of patients with sarcoma. Bone sarcomas had lower passing rates at 65.3% (n = 32 of 49) compared with soft tissue sarcomas at 76.7% (n = 263 of 343; P = .0008). Biopsy location also correlated with profiling efficiency. Bone biopsy specimens had a 52.8% (n = 19 of 36) passing rate versus lung (61.1%; n = 33 of 54) and abdomen (80.1%; n = 109 of 136) specimens. CGP altered physician treatment selection in 25% of evaluable patients (n = 7 of 28) and was associated with improved progression-free survival. CONCLUSION To our knowledge, this is the largest technical evaluation of the performance of CGP in sarcoma. CGP was effectively performed in the vast majority of sarcoma samples and altered physician treatment selection. Tumor location and tissue subtype were key determinants of profiling success and associated with preanalytic variables that affect DNA and RNA quality. These results support standardized biopsy collection protocols to improve profiling outcomes.

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Comprehensive Genomic Profiling of Adult Renal Sarcomas Provides Insight into Disease Biology and Opportunities for Targeted Therapies

Cited by 7 publications

References 33 publications

Report of two primary renal tumors with myxoid features. Differential diagnosis between benign and malignant entities

Report of two primary renal tumors with myxoid features. Differential diagnosis between benign and malignant entities

Primary Adult Retroperitoneal Sarcoma: A Comprehensive Genomic Profiling Study

Identifying Opportunities and Challenges for Patients With Sarcoma as a Result of Comprehensive Genomic Profiling of Sarcoma Specimens

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