Germline Mutation Landscape and Associated Clinical Characteristics in Chinese Patients With Renal Cell Carcinoma

BackgroundRenal cell carcinoma (RCC) is a disease of genomic alterations, of which the complete panorama helps in facilitating molecular-guided therapy. Germline mutation profiles and associated somatic and clinical characteristics remains unexplored in Chinese RCC patients.MethodsWe retrospectively profiled the germline and somatic mutations of 322 unselected RCC patients using a panel consisting of 808 cancer-related genes. We categorized patients into three groups based on germline mutation status and compared the somatic mutation spectrum among different groups.ResultsApproximately one out of ten (9.9%) RCC patients were identified to carry pathogenic/likely pathogenic (P/LP) germline variants (PGVs), of which 3.7% were variants in syndromic RCC-associated genes and 6.2% were other cancer-predisposition genes. The most common PGV was found in VHL (2.2%), followed by FH, TSC2, ATM, BRCA1, NBN, and BLM (0.6% each). Young patients (≤46 years) were more likely to harbor PGVs. Variants in syndromic RCC-associated genes were predominant identified in young patients, while variants in other cancer-predisposition genes were found in patients >46 years more frequently. Furthermore, 39.3% (11/28) of patients carrying PGVs were detected to have somatic “second hit” events. Germline and somatic sequencing, including microsatellite instability (MSI) status analysis, provided potentially actionable therapeutic targets in 17.1% of patients in the whole cohort.ConclusionsOur results revealed that approximately 10% of RCC patients carried clinically significant germline mutations. Current guidelines recommendation for genetic testing seemed not sensitive enough to identify patients with hereditary RCC susceptibility. It is rational to promote genetic testing in RCC population.

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Clinical characteristics and genetic testing of an atypical familial von Hippel-Lindauzon renal cell carcinoma

Annals of Translational Medicine ◽

10.21037/atm.2019.10.09 ◽

2019 ◽

Vol 7 (22) ◽

pp. 677-677

Author(s):

Jing Wang ◽

Feng Qi ◽

Ping Zhang ◽

Zicheng Xu ◽

Yuxiao Zheng ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Genetic Testing ◽

Cell Carcinoma ◽

Renal Cell ◽

Clinical Characteristics

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Clinical characteristics and treatments of hereditary leiomyomatosis renal cell carcinoma: two case reports and literature review

Aktuelle Urologie ◽

10.1055/a-1139-0697 ◽

2020 ◽

Author(s):

Dalin Feng ◽

Mingshuai Wang ◽

Xiaodong Zhang ◽

Jianwen Wang

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Female Patient ◽

Male Patient ◽

Renal Cell ◽

Clinical Characteristics ◽

Genetic Test ◽

Enhanced Ct ◽

The Right ◽

Hereditary Leiomyomatosis

Abstract Background The objective of this study is to discuss clinical characteristics and treatments of hereditary leiomyomatosis renal cell carcinoma on the basis of 2 cases and to review recent literature, in order to present medical advances. Methods A 29-year old male patient came to our hospital because of a huge tumour on the right kidney. Enhanced CT showed that the tumour was about 15.5*10.5 cm, and was considered to be malignant. Another case was a 38-year old female patient. She complained was found to have a right kidney tumour in a routine physical examination. Enhanced CT showed an early-stage tumour of about 4.3*3.7 cm on the lower pole of the right kidney. The male patient underwent open radical nephrectomy and the female patient underwent laparoscopic radical nephrectomy and extensive retroperitoneal lymph node dissection. The two patients underwent genetic testing and were diagnosed as having hereditary leiomyomatosis with renal cell carcinoma. Results The postoperative pathology in both patients revealed type 2 papillary renal cell carcinoma but with different prognosis. The male patient suffered multiple metastasis 10 months post-operation. The metastatic tumour of the abdominal wall was resected to confirm recurrence and hereditary leiomyomatosis renal cell carcinoma was diagnosed by the genetic test. While the female patient had a specific family history and uterine leiomyomas, the genetic test helped us to identify hereditary leiomyomatosis renal cell carcinoma pre-operation. Because of the early diagnosis and timely treatment, the female patient was considered to have a good prognosis. Conclusion Hereditary leiomyomatosis renal cell carcinoma is a rare hereditary disease resulting from FH gene mutation. There are currently no effective treatments.Our cases demonstrate that hereditary leiomyomatosis renal cell carcinoma is a very aggressive disease. Early screening and surveillance are recommended for patients with a family history or who are at risk of hereditary leiomyomatosis renal cell carcinoma. Surgical and palliative therapy still play an important role in clinical treatment.

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PD12-03 ASSOCIATION OF PARTIAL AND RADICAL NEPHRECTOMY ON SURVIVAL IN YOUNG PATIENTS WITH NON-CLEAR CELL RENAL CELL CARCINOMA

The Journal of Urology ◽

10.1016/j.juro.2018.02.639 ◽

2018 ◽

Vol 199 (4S) ◽

Author(s):

Kristian Stensland ◽

Jared Schober ◽

David Canes ◽

Navneet Ramesh ◽

Brendan Waldoch ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Radical Nephrectomy ◽

Clear Cell ◽

Young Patients ◽

Cell Renal Cell Carcinoma

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Association of BMI, body composition and outcomes in Chinese patients with metastatic renal cell carcinoma treated with immunotherapy: A retrospective, multicohort analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16563 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16563-e16563

Author(s):

Jun Wang ◽

Yuanyuan Qu ◽

Wenhao Xu ◽

Chunping Yu ◽

Zhiling Zhang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Body Composition ◽

Cell Carcinoma ◽

Renal Cell ◽

Normal Weight ◽

Chinese Patients ◽

Tissue Area ◽

Subcutaneous Adipose ◽

High Bmi

e16563 Association of BMI, body composition and outcomes in Chinese patients with metastatic renal cell carcinoma treated with immunotherapy: a retrospective, multicohort analysis. Background: Obesity (body-mass index [BMI] ≥30 kg/m) is associated with a higher risk of developing clear cell renal cell carcinoma (RCC) but, paradoxically, obesity is also associated with better outcome in renal cell carcinoma (RCC) patients treated with immunotherapy. Whether BMI associate outcomes in Chinese RCC patients treated with immunotherapy considering Asian population has a lower BMI? In this study, we aimed to investigate the relationship between BMI, body composition and outcomes of Chinese patients with RCC treated with immunotherapy. Methods: We evaluated clinical data of metastatic RCC patients treated with immunotherapy from five major centers in China. Despite using the Chinese standard, only 6 people met the obese standard (BMI ≥28 kg/m, as per WHO's BMI categories), so we divided the patients into high BMI gourps (BMI ≥24.0 kg/m), and normal weight groups (BMI 18.5-23·9 kg/m). We assessed overall survival, defined as the time from treatment initiation to the date of any-cause death or of censoring on the day of the last follow-up, in high BMI patients and in patients with a normal weight. We also investigative the relationship between body composition (skeletal muscle index (SMI = skeletal muscle area/height2), skeletal muscle density (SMD), and subcutaneous adipose distribution index (SADI = subcutaneous adipose tissue area / subcutaneous adipose tissue area + visceral adipose tissue area) of each patient at the third lumbar vertebrae) and overall survival using CT or MRI scan at the treatment initiation. Results: Out of a total of 222 patients, 203 had evaluable CT or MRI radiographs, pretreatment BMI measurements, and overall survival data for analyses, and we excluded 4 (1.7%) underwetight patients, leaving a final cohort of 199 patients from this study for our analyses. There were 79 (39.7%) high BMI patients and 120 (65.3%) normal weight patients. There was no difference in overall survival between the high BMI and normal weight groups (HR:1.36, CI 0.83-2.21). In addition, SMI and SMD were not associated with outcome of patients. Interestingly, although there was no statistical difference, subcutaneous fat was associated with better outcomes, while visceral fat was associated with poor outcomes. Thus, the combination of the two indicators, SADI, showed a significant prognostic correlation after adjustment for International Metastatic RCC Database risk score (aHR:0.314, CI 0.19-0.51). Conclusions: BMI is not a good predictor of the outcome of immunotherapy in Chinese patients with RCC. Evaluation of body composition may be a better tool for predicting prognosis in RCC patients treated with immunotherapy.

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