Familial kidney cancer: Implications of new syndromes and molecular insights Journal Article

Authors: Carlo, M. I.; Hakimi, A. A.; Stewart, G. D.; Bratslavsky, G.; Brugarolas, J.; Chen, Y. B.; Linehan, W. M.; Maher, E. R.; Merino, M. J.; Offit, K.; Reuter, V. E.; Shuch, B.; Coleman, J. A.
Article Title: Familial kidney cancer: Implications of new syndromes and molecular insights
Abstract: Context: Hereditary cases account for about 5% of all cases of renal cell carcinoma (RCC). With advances in next-generation sequencing, several new hereditary syndromes have been described in the last few years. Objective: To review and summarise the recent preclinical and clinical literature in hereditary renal cancer. Evidence acquisition: A systematic review of the literature was performed in November 2018 using PubMed and OMIM databases, with an emphasis on kidney cancer, genetics and genomics, clinical criteria, and management. Evidence synthesis: Several autosomal dominant hereditary RCC syndromes have been described, including those related to germline pathogenic variants in VHL, MET, FH, TSC1/TSC2, FLCN, SDHA/B/C/D, BAP1, CDC73, and MITF. Clinical spectrum of SDH, BAP1, and MITF is still being defined, although these appear to be associated with a lower incidence of RCC. FH and likely BAP1 RCC are associated with more aggressive disease. Preclinical and clinical studies show that using systemic therapy that exploits specific genetic pathways is a promising strategy. Conclusions: There are several well-described hereditary RCC syndromes, as well as recently identified ones, for which the full clinical spectrum is yet to be defined. In the new era of precision medicine, identification of these syndromes may play an important role in management and systemic treatment selection. Patient summary: This review covers updates in the diagnosis and management of familial kidney cancer syndromes. We describe updates in testing and management of the most common syndromes such as von Hippel-Lindau, and hereditary leiomyomatosis and renal cell carcinoma. We also provide insights into recently described familial kidney cancer syndromes. © 2019 European Association of Urology In the last few years, there have been significant advances in our knowledge about the familial kidney cancer syndromes, with updated recommendations on work-up and management. Additionally, there are more recently described familial kidney cancer syndromes that may be under-recognised. © 2019 European Association of Urology
Keywords: clinical feature; review; genetic variability; renal cell carcinoma; cancer genetics; systematic review; hamartin; tuberin; genomics; radiography; hereditary leiomyomatosis renal cell carcinoma; birt hogg dube syndrome; kidney cancer; leiomyomatosis; von hippel lindau disease; von hippel-lindau disease; microphthalmia associated transcription factor; von hippel lindau protein; scatter factor receptor; fumarate hydratase; succinate dehydrogenase; autosomal dominant inheritance; tuberous sclerosis complex; hereditary cancer; genetic counselling; human; priority journal; hereditary tumor syndrome; birt-hogg-dubé syndrome; hereditary papillary renal cell carcinoma; bap1 tumour predisposition syndrome; hereditary paraganglioma pheochromocytoma syndrome
Journal Title: European Urology
Volume: 76
Issue: 6
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2019-12-01
Start Page: 754
End Page: 764
Language: English
DOI: 10.1016/j.eururo.2019.06.015
PUBMED: 31326218
PROVIDER: scopus
Notes: Review -- Export Date: 2 December 2019 -- Source: Scopus
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MSK Authors
  1. Jonathan Coleman
    206 Coleman
  2. Kenneth Offit
    572 Offit
  3. Yingbei Chen
    264 Chen
  4. Victor Reuter
    1015 Reuter
  5. Abraham Ari Hakimi
    170 Hakimi
  6. Maria Isabel Carlo
    42 Carlo