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

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.

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Ovarian metastasis of clear cell renal cell carcinoma: A case report

Canadian Urological Association Journal ◽

10.5489/cuaj.1456 ◽

2014 ◽

Vol 8 (3-4) ◽

pp. 188 ◽

Cited By ~ 4

Author(s):

Lenka Bauerová ◽

Pavel Dundr ◽

Daniela Fischerová ◽

Michal Pešl ◽

Michal Zikán ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Left Kidney ◽

Progesterone Receptors ◽

Ovarian Tumour ◽

Tumour Mass ◽

Cell Renal Cell Carcinoma ◽

History Of

We report on a 61-year-old woman with a history of right-sided nephrectomy for clear cell renal cell carcinoma (RCC) occurring 21 years ago; she currently presented with a bilateral ovarian tumour. Histologically, the tumour of both ovaries was clear cell carcinoma. Immunohistochemically, the tumour cells were positive for vimentin, RCC marker, epithelial membrane antigen, cytokeratin AE1/3 and CD10. Cytokeratin 7, CA125, HMWCK, estrogen and progesterone receptors were all negative. Based on the morphologyand immunophenotype of the tumour, we established a diagnosis of late metastasis of RCC in the ovaries. A postoperative abdominal computed tomography scan, however, revealed a tumour mass solely in the left kidney, which had not been visible in the preoperative ultrasound. The patient underwent nephron-sparing surgery and a biopsy showed the tumour to be clear cell RCC. Metastasis of RCC to the ovaries is rare, and to the best of our knowledge, only 24 cases have been reported to date. However, due to the different treatments and prognosis, the distinction between a primary ovarian tumour and metastasis of RCC is important.

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Paraneoplastic limbic encephalitis cured with nephron-sparing surgery in a patient with clear cell renal cell carcinoma: a case report

Journal of International Medical Research ◽

10.1177/0300060519863524 ◽

2019 ◽

Vol 47 (10) ◽

pp. 5318-5322

Author(s):

Lunfeng Zhu ◽

Xiaolin Deng ◽

Zhaohui Lai ◽

Ning Xie ◽

Wanlong Tan

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Limbic Encephalitis ◽

Nephron Sparing Surgery ◽

Cell Renal Cell Carcinoma ◽

Paraneoplastic Limbic Encephalitis ◽

Nephron Sparing ◽

History Of

Paraneoplastic limbic encephalitis (PLE) in association with clear cell renal cell carcinoma has never been reported in China. We herein describe a 54-year-old man with a 1-week history of headache and a 3-day history of psychiatric symptoms. Slight nuchal rigidity was found by physical examination. Imaging studies of the head were normal. Blood and cerebrospinal fluid antibody testing were both positive for N-methyl-D-aspartic acid antibodies. Subsequent contrast-enhanced computed tomography revealed a 5.2- × 4.2-cm left kidney mass with intense enhancement. Emergent laparoscopic nephron-sparing surgery was successfully performed. Immunohistochemistry revealed clear cell renal cell carcinoma. The patient’s status improved after the surgery, and he was discharged after 1 month of hospitalization. At the 6-month follow-up, magnetic resonance imaging showed no recurrence, and the patient was living independently. This case indicates the potential effect of nephron-sparing surgery in the treatment of PLE. Tumor screening should be performed early in patients with suspected PLE. Early surgical resection of the primary tumor can improve patients’ prognosis.

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Rare Case of Clear Cell Renal Cell Carcinoma Metastasizing to Contralateral Kidney and Ipsilateral Parotid more than five Years following Nephrectomy

Balkan Journal of Dental Medicine ◽

10.2478/bjdm-2019-0020 ◽

2019 ◽

Vol 23 (2) ◽

pp. 108-111

Author(s):

Guy Sydney ◽

Kalliopi Ioakim ◽

Nayia Kara ◽

George Pantelas

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Rare Case ◽

Clear Cell ◽

Histopathological Diagnosis ◽

Cell Renal Cell Carcinoma ◽

Contralateral Kidney ◽

History Of ◽

Patient’S History

Summary Backgroung/Aim: Salivary gland malignancies are rare, with only a fraction due to metastases. We report a rare case of the Clear Cell Renal Cell Carcinoma (CCRCC), a subtype of the Renal Cell Carcinoma (RCC), metastasizing to the parotid gland more than five years following nephrectomy. Case report: A 75-year-old female presented with a unilateral left parotid mass that was growing over the period of 18 months. After clinical and laboratory examinations, the patient underwent left partial superficial parotidectomy with preservation of the facial nerve. The significance of the patient’s history of the CCRCC was pivotal to the histopathological diagnosis of a metastatic CCRCC to the parotid. Conclusions: The unpredictable nature of the RCC results in the need for a long period of follow-up, as well as having a high degree of suspicion of metastasis in a patient presenting with a medical history of the RCC and a parotid mass.

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

10.21203/rs.3.rs-48012/v2 ◽

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.

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Granulomata in Clear Cell Renal Cell Carcinoma: An Uncommon Presentation of a Common Cancer, Not Two Separate Entities

Clinical Pathology ◽

10.1177/2632010x20954215 ◽

2020 ◽

Vol 13 ◽

pp. 2632010X2095421

Author(s):

Daniel Hugh Russell

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Prognostic Significance ◽

Cell Renal Cell Carcinoma ◽

Uncommon Presentation ◽

History Of ◽

Relative Rarity ◽

Tumor Types

Sarcoidal-like granulomata (SLG) are known to occur as a response to a variety of tumor types, including lymphomas, prominently seminoma, other miscellaneous carcinomas, and rarely in renal cell carcinoma. There have been a handful of previously reported cases in the literature of SLG occurring in association with RCC. Of those previously reported, none were associated with infection and only 3 patients had a history of sarcoidosis. The prognostic significance of SLG in RCC is unsettled and somewhat complicated by the relative rarity of its occurrence and the paucity of data therein. A case is presented of an otherwise histologically typical clear cell renal cell carcinoma with peri-tumoral and intra-tumoral SLG. Special stains were negative for organisms and past medical history was negative for sarcoidosis and connective tissue disease.

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Natural history of Von Hippel–Lindau disease-associated and sporadic clear cell renal cell carcinoma: a comparative study

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03806-0 ◽

2021 ◽

Author(s):

Jie Wang ◽

Lei Zhang ◽

Jianhui Qiu ◽

Ziao Li ◽

Yucai Wu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Natural History ◽

Comparative Study ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Von Hippel Lindau ◽

History Of ◽

Von Hippel Lindau Disease

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

10.21203/rs.3.rs-48012/v3 ◽

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.

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

10.21203/rs.3.rs-48012/v1 ◽

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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