scholarly journals Pathogenic germline variants in patients with features of hereditary renal cell carcinoma: Evidence for further locus heterogeneity

2020 ◽  
Vol 60 (1) ◽  
pp. 5-16 ◽  
Author(s):  
Philip S. Smith ◽  
Hannah West ◽  
James Whitworth ◽  
Bruce Castle ◽  
Francis H. Sansbury ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Locus Heterogeneity ◽  
Germline Variants

scholarly journals 8q24 clear cell renal cell carcinoma germline variant is associated with VHL mutation status and clinical aggressiveness

BMC Urology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jeanette E. Eckel-Passow ◽  
Huihuang Yan ◽  
Matthew L. Kosel ◽  
Daniel Serie ◽  
Paul A. Decker ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Mutation Status ◽  
Germline Variants ◽  
Tumor Genetics

Abstract Background The four most commonly-mutated genes in clear cell renal cell carcinoma (ccRCC) tumors are BAP1, PBRM1, SETD2 and VHL. And, there are currently 14 known RCC germline variants that have been reproducibly shown to be associated with RCC risk. However, the association of germline genetics with tumor genetics and clinical aggressiveness are unknown. Methods We analyzed 420 ccRCC patients from The Cancer Genome Atlas. Molecular subtype was determined based on acquired mutations in BAP1, PBRM1, SETD2 and VHL. Aggressive subtype was defined clinically using Mayo SSIGN score and molecularly using the ccA/ccB gene expression subtype. Publically-available Hi-C data were used to link germline risk variants with candidate target genes. Results The 8q24 variant rs35252396 was significantly associated with VHL mutation status (OR = 1.6, p = 0.0037) and SSIGN score (OR = 1.9, p = 0.00094), after adjusting for multiple comparisons. We observed that, while some germline variants have interactions with nearby genes, some variants demonstrate long-range interactions with target genes. Conclusions These data further demonstrate the link between rs35252396, HIF pathway and ccRCC clinical aggressiveness, providing a more comprehensive picture of how germline genetics and tumor genetics interact with respect to tumor development and progression.

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 Trans-ethnic variation in germline variants of patients with renal cell carcinoma

Cell Reports ◽  
2021 ◽  
Vol 34 (13) ◽  
pp. 108926
Author(s):  
Sarah Abou Alaiwi ◽  
Amin H. Nassar ◽  
Elio Adib ◽  
Stefan M. Groha ◽  
Elie W. Akl ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Ethnic Variation ◽  
Germline Variants

scholarly journals Analysis of Germline Variants in CDH1, IGFBP3, MMP1, MMP3, STK15 and VEGF in Familial and Sporadic Renal Cell Carcinoma

PLoS ONE ◽  
2009 ◽  
Vol 4 (6) ◽  
pp. e6037 ◽  
Author(s):  
Christopher Ricketts ◽  
Maurice P. Zeegers ◽  
Jan Lubinski ◽  
Eamonn R. Maher
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Germline Variants ◽  
Sporadic Renal Cell Carcinoma

Prevalence of pathogenic germline variants in patients with metastatic renal cell carcinoma

2021 ◽  
Author(s):  
María Santos ◽  
Javier Lanillos ◽  
Juan María Roldan-Romero ◽  
Eduardo Caleiras ◽  
Cristina Montero-Conde ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Germline Variants

scholarly journals Clear Cell Papillary Renal Cell Carcinoma Shares Distinct Molecular Characteristics and may be Significantly Associated With Higher Risk of Developing Second Primary Malignancy

2021 ◽  
Vol 27 ◽  
Author(s):  
Xi Tian ◽  
Wen-Hao Xu ◽  
Jun-Long Wu ◽  
Hua-Lei Gan ◽  
Hong-Kai Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Papillary Renal Cell Carcinoma ◽  
Second Primary ◽  
Published Data ◽  
Second Primary Malignancy ◽  
Primary Malignancy ◽  
Germline Variants

Traditionally, clear cell papillary renal cell carcinoma (ccpRCC) was considered to share similar molecular and histological characteristics with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Here we aimed to identify somatic and germline variants of ccpRCC. For this purpose, we conducted whole-exome sequencing to detect somatic variants in the tissues of 18 patients with pathologically confirmed ccpRCC, who underwent surgical treatment at Fudan University Shanghai Cancer Center. Targeted sequencing was conducted to detect germline variants in paired tumor or normal tissues or blood. Somatic and germline variants of ccRCC and Renal cell carcinoma included in The Cancer Genome Atlas data and other published data were analyzed as well. The molecular profiles of ccpRCC, ccRCC and pRCC were compared. Among the 387 somatic variants identified, TCEB1 (3/18) and VHL (3/18) variants occurred at the highest frequencies. Germline mutation detection showed that nine variants associated with Fanconi anemia (VAFAs) pathway (FANCA, 6/18; FANCI, 3/18) were identified in 18 ccpRCC patients. Among ccpRCC patients with VAFAs, five out of eight patients had second primary malignancy or family history of cancer. Somatic variants characteristics may distinguish ccpRCC from ccRCC or pRCC and germline VAFAs may be a molecular characterization of ccpRCC. Compared with ccRCC or pRCC, ccpRCC patients may be significantly correlated with higher risk of developing second primary malignancy.

scholarly journals 8q24 Clear Cell Renal Cell Carcinoma Germline Variant is Associated with VHL Mutation Status and Clinical Aggressiveness

2020 ◽  
Author(s):  
Jeanette E Eckel-Passow ◽  
Huihuang Yan ◽  
Matthew Kosel ◽  
Daniel Serie ◽  
Robert Jenkins ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Mutation Status ◽  
Germline Variants ◽  
Tumor Genetics

Abstract Background The four most commonly-mutated genes in clear cell renal cell carcinoma (ccRCC) tumors are BAP1 , PBRM1 , SETD2 and VHL . And, there are currently 14 known RCC germline variants that have been reproducibly shown to be associated with RCC risk. However, the association of germline genetics with tumor genetics and clinical aggressiveness are unknown. Methods We analyzed 420 ccRCC patients from The Cancer Genome Atlas (TCGA). Molecular subtype was determined based on acquired mutations in BAP1 , PBRM1 , SETD2 and VHL . Aggressive subtype was defined clinically using Mayo SSIGN score and molecularly using the ccA/ccB gene expression subtype. Publically-available Hi-C data were used to link germline risk variants with candidate target genes. Results The 8q24 variant rs35252396 was significantly associated with VHL mutation status (OR=1.6, p=0.0037) and SSIGN score (OR=1.9, p=0.00094), after adjusting for multiple comparisons. We observed that, while some germline variants have interactions with nearby genes, some variants demonstrate long-range interactions with target genes. Conclusions These data further demonstrate the link between rs35252396, HIF pathway and ccRCC clinical aggressiveness, providing a more comprehensive picture of how germline genetics and tumor genetics interact with respect to tumor development and progression.

scholarly journals Interaction of germline variants in a family with a history of early‐onset clear cell renal cell carcinoma

2019 ◽  
Vol 7 (3) ◽  
pp. e556 ◽  
Author(s):  
Emmanuelle Nicolas ◽  
Elena V. Demidova ◽  
Waleed Iqbal ◽  
Ilya G. Serebriiskii ◽  
Ramilia Vlasenkova ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Early Onset ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Germline Variants ◽  
History Of

scholarly journals 8q24 Clear Cell Renal Cell Carcinoma Germline Variant is Associated with VHL Mutation Status and Clinical Aggressiveness

2020 ◽  
Author(s):  
Jeanette E Eckel-Passow ◽  
Huihuang Yan ◽  
Matthew Kosel ◽  
Daniel Serie ◽  
Paul Decker ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Mutation Status ◽  
Germline Variants ◽  
Tumor Genetics

Abstract Background: The four most commonly-mutated genes in clear cell renal cell carcinoma (ccRCC) tumors are BAP1, PBRM1, SETD2 and VHL. And, there are currently 14 known RCC germline variants that have been reproducibly shown to be associated with RCC risk. However, the association of germline genetics with tumor genetics and clinical aggressiveness are unknown.Methods: We analyzed 420 ccRCC patients from The Cancer Genome Atlas (TCGA). Molecular subtype was determined based on acquired mutations in BAP1, PBRM1, SETD2 and VHL. Aggressive subtype was defined clinically using Mayo SSIGN score and molecularly using the ccA/ccB gene expression subtype. Publically-available Hi-C data were used to link germline risk variants with candidate target genes. Results: The 8q24 variant rs35252396 was significantly associated with VHL mutation status (OR=1.6, p=0.0037) and SSIGN score (OR=1.9, p=0.00094), after adjusting for multiple comparisons. We observed that, while some germline variants have interactions with nearby genes, some variants demonstrate long-range interactions with target genes.Conclusions: These data further demonstrate the link between rs35252396, HIF pathway and ccRCC clinical aggressiveness, providing a more comprehensive picture of how germline genetics and tumor genetics interact with respect to tumor development and progression.

scholarly journals 8q24 Clear Cell Renal Cell Carcinoma Germline Variant is Associated with VHL Mutation Status and Clinical Aggressiveness

2020 ◽  
Author(s):  
Jeanette E Eckel-Passow ◽  
Huihuang Yan ◽  
Matthew Kosel ◽  
Daniel Serie ◽  
Paul A. Decker ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Mutation Status ◽  
Germline Variants ◽  
Tumor Genetics

Abstract Background: The four most commonly-mutated genes in clear cell renal cell carcinoma (ccRCC) tumors are BAP1, PBRM1, SETD2 and VHL. And, there are currently 14 known RCC germline variants that have been reproducibly shown to be associated with RCC risk. However, the association of germline genetics with tumor genetics and clinical aggressiveness are unknown.Methods: We analyzed 420 ccRCC patients from The Cancer Genome Atlas (TCGA). Molecular subtype was determined based on acquired mutations in BAP1, PBRM1, SETD2 and VHL. Aggressive subtype was defined clinically using Mayo SSIGN score and molecularly using the ccA/ccB gene expression subtype. Publically-available Hi-C data were used to link germline risk variants with candidate target genes. Results: The 8q24 variant rs35252396 was significantly associated with VHL mutation status (OR=1.6, p=0.0037) and SSIGN score (OR=1.9, p=0.00094), after adjusting for multiple comparisons. We observed that, while some germline variants have interactions with nearby genes, some variants demonstrate long-range interactions with target genes.Conclusions: These data further demonstrate the link between rs35252396, HIF pathway and ccRCC clinical aggressiveness, providing a more comprehensive picture of how germline genetics and tumor genetics interact with respect to tumor development and progression.

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