Growth Rates of Genetically Defined Renal Tumors: Implications for Active Surveillance and Intervention

Ball, Mark W.; An, Julie Y.; Gomella, Patrick T.; Gautam, Rabindra; Ricketts, Christopher J.; Vocke, Cathy D.; Schmidt, Laura S.; Merino, María J.; Srinivasan, Ramaprasad; Metwalli, Adam R.; Linehan, W. Marston

doi:10.1200/jco.19.02263

Cited by 42 publications

(25 citation statements)

References 33 publications

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“…Even young family members should consider genetic testing as uveal and ocular melanomas may present as early as in the teenage years ( 6 , 21 ). Screening renal ultrasound, MRI, or urinalysis for renal cell carcinoma could also be considered ( 21 ), as these patients are prone to renal cell carcinoma and BAP1 mutated renal tumors appear to grow at a faster rate than kidney cancers driven by other mutations such as in von Hippel-Lindau disease ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Germline BAP1 Mutation in a Family With Multi-Generational Meningioma With Rhabdoid Features: A Case Series and Literature Review

et al. 2021

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Meningioma is the most common primary brain tumor, and recurrence risk increases with increasing WHO Grade from I to III. Rhabdoid meningiomas are a subset of WHO Grade III tumors with rhabdoid cells, a high proliferation index, and other malignant features that follow an aggressive clinical course. Some meningiomas with rhabdoid features either only focally or without other malignant features are classified as lower grade yet still recur early. Recently, inactivating mutations in the tumor suppressor gene BAP1 have been associated with poorer prognosis in rhabdoid meningioma and meningioma with rhabdoid features, and germline mutations have been linked to a hereditary tumor predisposition syndrome (TPDS) predisposing patients primarily to melanoma and mesothelioma. We present the first report of a familial BAP1 inactivating mutation identified after multiple generations of a family presented with meningiomas with rhabdoid features instead of with previously described BAP1 loss-associated malignancies. A 24-year-old female presented with a Grade II meningioma with rhabdoid and papillary features treated with subtotal resection, adjuvant external beam radiation therapy, and salvage gamma knife radiosurgery six years later. Around that time, her mother presented with a meningioma with rhabdoid and papillary features managed with resection and adjuvant radiation therapy. Germline testing was positive for a pathogenic BAP1 mutation in both patients. Sequencing of both tumors demonstrated biallelic BAP1 inactivation via the combination of germline BAP1 mutation and either loss of heterozygosity or somatic mutation. No additional mutations implicated in oncogenesis were noted from either patient’s germline or tumor sequencing, suggesting that the inactivation of BAP1 was responsible for pathogenesis. These cases demonstrate the importance of routine BAP1 tumor testing in meningioma with rhabdoid features regardless of grade, germline testing for patients with BAP1 inactivated tumors, and tailored cancer screening in this population.

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Section: Discussionmentioning

confidence: 99%

Germline BAP1 Mutation in a Family With Multi-Generational Meningioma With Rhabdoid Features: A Case Series and Literature Review

et al. 2021

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“…In a study of 292 genetically defined patients, growth rates were analyzed from 435 tumors. Bap1-deficient tumors had the fastest growth rate (median 0.6 cm/year), while tumors with MET-activated tumors had the slowest growth rate (0.015 cm/year) [ 56 ].…”

Section: Clinical Managementmentioning

confidence: 99%

Precision Surgery and Kidney Cancer: Knowledge of Genetic Alterations Influences Surgical Management

Gomella

Linehan

Ball

2021

Genes

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Renal cell carcinoma is a term that represents multiple different disease processes, each driven by different genetic alterations, with distinct histology, and biological potential which necessitates divergent management strategies. This review discusses the genetic alterations seen in several forms of hereditary kidney cancer and how that knowledge can dictate when and how to intervene with a focus on the surgical management of these tumors.

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“…The evaluation of the growth rates of a cohort of 292 patients with genetically defined renal tumors and showed that BAP1-deficient tumors are those growing at the fastest rates [ 38 ].…”

Section: Hereditary Bap1 Tumor Syndromementioning

confidence: 99%

Genetic Alterations in Renal Cancers: Identification of The Mechanisms Underlying Cancer Initiation and Progression and of Therapeutic Targets

Testa

Castelli

2020

Medicines

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Renal cell cancer (RCC) involves three most recurrent sporadic types: clear-cell RCC (70–75%, CCRCC), papillary RCCC (10–15%, PRCC), and chromophobe RCC (5%, CHRCC). Hereditary cases account for about 5% of all cases of RCC and are caused by germline pathogenic variants. Herein, we review how a better understanding of the molecular biology of RCCs has driven the inception of new diagnostic and therapeutic approaches. Genomic research has identified relevant genetic alterations associated with each RCC subtype. Molecular studies have clearly shown that CCRCC is universally initiated by Von Hippel Lindau (VHL) gene dysregulation, followed by different types of additional genetic events involving epigenetic regulatory genes, dictating disease progression, aggressiveness, and differential response to treatments. The understanding of the molecular mechanisms that underlie the development and progression of RCC has considerably expanded treatment options; genomic data might guide treatment options by enabling patients to be matched with therapeutics that specifically target the genetic alterations present in their tumors. These new targeted treatments have led to a moderate improvement of the survival of metastatic RCC patients. Ongoing studies based on the combination of immunotherapeutic agents (immune check inhibitors) with VEGF inhibitors are expected to further improve the survival of these patients.

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Growth Rates of Genetically Defined Renal Tumors: Implications for Active Surveillance and Intervention

Cited by 42 publications

References 33 publications

Germline BAP1 Mutation in a Family With Multi-Generational Meningioma With Rhabdoid Features: A Case Series and Literature Review

Germline BAP1 Mutation in a Family With Multi-Generational Meningioma With Rhabdoid Features: A Case Series and Literature Review

Precision Surgery and Kidney Cancer: Knowledge of Genetic Alterations Influences Surgical Management

Genetic Alterations in Renal Cancers: Identification of The Mechanisms Underlying Cancer Initiation and Progression and of Therapeutic Targets

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