Clinical and pathological impact of <i>VHL, PBRM1, BAP1, SETD2, KDM6A</i>, and <i>JARID1c</i> in clear cell renal cell carcinoma

Gossage, Lucy; Murtaza, Muhammed; Slatter, Andrew F.; Lichtenstein, Conrad; Warren, Anne Y.; Haynes, Beverley; Marass, Francesco; Roberts, Ian; Shanahan, Susan J.; Claas, Andreas; Dunham, Andrew; May, Andrew P.; Rosenfeld, Nitzan; Forshew, Tim; Eisen, Tim

doi:10.1002/gcc.22116

Cited by 114 publications

(103 citation statements)

References 68 publications

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“…Previous studies indicated that SETD2 mutation occurred in 3-12% of sporadic ccRCC patients, which ranked second of the most frequent gene mutations in ccRCC next to VHL gene mutation (17). In our present study, IHC staining revealed that SETD2 was positively expressed in the cell nucleus of all normal renal tubular tissues.…”

Section: Discussionsupporting

confidence: 65%

Loss of SETD2, but not H3K36me3, correlates with aggressive clinicopathological features of clear cell renal cell carcinoma patients

Liu

Guo

Zhang

et al. 2017

BST

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Section: Discussionsupporting

confidence: 65%

Loss of SETD2, but not H3K36me3, correlates with aggressive clinicopathological features of clear cell renal cell carcinoma patients

Liu

Guo

Zhang

et al. 2017

BST

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“…12 The deletion or mutation of BAP1 is associated with high tumor grade and poorer prognosis. [15][16][17][18] Following prior investigations for image-based inference of gene mutation status in glioblastoma multiforme brain tumors, lung, and breast tumors, we sought to investigate if BAP1 mutation status can be detected based on computationally derived volumetric and textural image features of the primary tumor from contrast enhanced renal CT scans of these patients. In this paper, we present an imaging-genomic pipeline to extract three-dimensional image features and correlate them with molecular data associated with the disease.…”

Section: Renal Cell Carcinomamentioning

confidence: 99%

Imaging-genomic pipeline for identifying gene mutations using three-dimensional intra-tumor heterogeneity features

et al. 2015

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Abstract. This paper presents an imaging-genomic pipeline to derive three-dimensional intra-tumor heterogeneity features from contrast-enhanced CT images and correlates them with gene mutation status. The pipeline has been demonstrated using CT scans of patients with clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas. About 15% of ccRCC cases reported have BRCA1-associated protein 1 (BAP1) gene alterations that are associated with high tumor grade and poor prognosis. We hypothesized that BAP1 mutation status can be detected using computationally derived image features. The molecular data pertaining to gene mutation status were obtained from the cBioPortal. Correlation of the image features with gene mutation status was assessed using the Mann-Whitney-Wilcoxon rank-sum test. We also used the random forests classifier in the Waikato Environment for Knowledge Analysis software to assess the predictive ability of the computationally derived image features to discriminate cases with BAP1 mutations for ccRCC. Receiver operating characteristics were obtained using a leave-one-out-cross-validation procedure. Our results show that our model can predict BAP1 mutation status with a high degree of sensitivity and specificity. This framework demonstrates a methodology for noninvasive disease biomarker detection from contrast-enhanced CT images.

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“…Mutation of VHL alone is not sufficient to cause RCC cases 13 . Recently, large scale targeted and whole exome sequencing studies of RCC have identified other frequently mutated genes including polybromo 1 (PBRM1) and SET domain containing 2 (SETD2) 13 . The PBRM1 is a tumor suppressor gene, located on the short (p) arm of chromosome 3 at position 21 2 .…”

Section: Introductionmentioning

confidence: 99%

“…Classically, RCC is characterized by inactivation of the VHL tumor suppressor gene in the majority of cases [11][12][13] . Mutation of VHL alone is not sufficient to cause RCC cases 13 .…”

Section: Introductionmentioning

confidence: 99%

Molecular genetics of renal cell carcinoma: polybromo 1 and set domain containing 2 genes

Ismaiel¹,

Mohammed²,

Hidayat³

2016

Cukurova Med J

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AbstractÖz Purpose: Renal cell carcinoma (RCC) is genetically characterized by the recurrent loss of the short arm of chromosome 3. Classically, Von Hippel Lindau (VHL) was the only frequently mutated gene in RCC. Recently, several novel frequent mutations of histone modifying and chromatin remodeling genes, including PBRM1 and SETD2, were identified. In the present study, we aimed to determine the possible relationship between PBRM1 and SETD2 genes, and renal cell carcinoma by molecular techniques. Material and Methods: Screening possible mutation and determining mRNA expression level of PBRM1 and SETD2 genes in 20 pairs of tumor and normal samples of RCC patients were performed by nucleotide sequencer and reverse transcription-polymerase chain reaction (RT-PCR). Results: The mRNA expression levels of both genes were significantly reduced in tumor samples when compared with the control samples. As a result of mutational analysis, a single insertion nucleotide polymorphism in exon 12 of SETD2 gene was detected in one patient. Conclusion: Reduced mRNA expression level of PBRM1 and SETD2 might be risk factor for RCC development. Further analysis is warranted to investigate responsible genes rather than PBRM1 and SETD2 in RCC. Amaç:Renal hücreli karsinoma (RCC) 3. kromozomun kısa kolundaki tekrar kayıpları ile karakterizedir. Klasik olarak Von Hippel Lindau sendromunda sadece RCC gen mutasyonu sıklıkla görülmekteydi. Son zamanlarda PBRM1 ve SETD2 yi içeren histon modifikasyon ve kromatin remodeling genlerinde de mutasyonlar yoğunlukla tanımlanmıştır. Bu çalışmada moleküler teknikler ile PBRM1 ve SETD2 genleri ile RCC arasındaki muhtemel ilişkiyi belirlenmesi amaçlanmıştır. Gereç ve Yöntem: RCC hastalarından alınan normal ve tümöral dokuda PBRM1 ve SETD2 genlerinin mRNA ekspresyon seviyeleri ve olası mutasyonları nükleotid sekanslama ve Reverse transkripsiyon polimeraz zincir reaksiyonu (RT-PCR) ile belirlendi. Bulgular: Kontrol ile kıyaslandığında her iki gen için de mRNA ekspresyon değerleri tümöral dokuda anlamlı derecede azalmıştır. Mutasyon analiz sonuçlarına göre 1 hastanın SETD2 geninin 12 nolu exonunda tek insersiyon nükleotid polimorfizmi saptandı. Sonuç: PBRM1 ve SETD2 mRNA ekspresyon seviyelerinin azalması RCC gelişmesi için risk faktörü olabilir. Gelecekte RCC de SETD2 ve PBRM1 in dışında farklı genlerinde araştırılması gerekmektedir.

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Clinical and pathological impact of VHL, PBRM1, BAP1, SETD2, KDM6A, and JARID1c in clear cell renal cell carcinoma

Cited by 114 publications

References 68 publications

Loss of SETD2, but not H3K36me3, correlates with aggressive clinicopathological features of clear cell renal cell carcinoma patients

Loss of SETD2, but not H3K36me3, correlates with aggressive clinicopathological features of clear cell renal cell carcinoma patients

Imaging-genomic pipeline for identifying gene mutations using three-dimensional intra-tumor heterogeneity features

Molecular genetics of renal cell carcinoma: polybromo 1 and set domain containing 2 genes

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