Familial Kidney Cancer: Implications of New Syndromes and Molecular Insights

Maria I. Carlo, A. Ari Hakimi, Grant D. Stewart, Gennady Bratslavsky, James B Brugarolas, Ying Bei Chen, W. Marston Linehan, Eamonn R. Maher, Maria J. Merino, Kenneth Offit, Victor E. Reuter, B. Shuch, Jonathan A. Coleman

Research output: Contribution to journalReview article

1 Citation (Scopus)

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. 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.

Original languageEnglish (US)
JournalEuropean urology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Kidney Neoplasms
Renal Cell Carcinoma
Leiomyomatosis
Genetic Databases
Precision Medicine
Genomics
PubMed
Databases
Incidence
Therapeutics

Keywords

  • Birt-Hogg-Dubé syndrome
  • Genetic counselling
  • Hereditary cancer
  • Hereditary leiomyomatosis renal cell carcinoma
  • Hereditary papillary renal cell carcinoma
  • Kidney cancer
  • Renal cell carcinoma
  • Tuberous sclerosis complex
  • von Hippel-Lindau disease

ASJC Scopus subject areas

  • Urology

Cite this

Carlo, M. I., Hakimi, A. A., Stewart, G. D., Bratslavsky, G., Brugarolas, J. B., Chen, Y. B., ... Coleman, J. A. (2019). Familial Kidney Cancer: Implications of New Syndromes and Molecular Insights. European urology. https://doi.org/10.1016/j.eururo.2019.06.015

Familial Kidney Cancer : Implications of New Syndromes and Molecular Insights. / Carlo, Maria I.; Hakimi, A. Ari; Stewart, Grant D.; Bratslavsky, Gennady; Brugarolas, James B; Chen, Ying Bei; Linehan, W. Marston; Maher, Eamonn R.; Merino, Maria J.; Offit, Kenneth; Reuter, Victor E.; Shuch, B.; Coleman, Jonathan A.

In: European urology, 01.01.2019.

Research output: Contribution to journalReview article

Carlo, MI, Hakimi, AA, Stewart, GD, Bratslavsky, G, Brugarolas, JB, Chen, YB, Linehan, WM, Maher, ER, Merino, MJ, Offit, K, Reuter, VE, Shuch, B & Coleman, JA 2019, 'Familial Kidney Cancer: Implications of New Syndromes and Molecular Insights', European urology. https://doi.org/10.1016/j.eururo.2019.06.015
Carlo, Maria I. ; Hakimi, A. Ari ; Stewart, Grant D. ; Bratslavsky, Gennady ; Brugarolas, James B ; Chen, Ying Bei ; Linehan, W. Marston ; Maher, Eamonn R. ; Merino, Maria J. ; Offit, Kenneth ; Reuter, Victor E. ; Shuch, B. ; Coleman, Jonathan A. / Familial Kidney Cancer : Implications of New Syndromes and Molecular Insights. In: European urology. 2019.
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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. 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.",
keywords = "Birt-Hogg-Dub{\'e} syndrome, Genetic counselling, Hereditary cancer, Hereditary leiomyomatosis renal cell carcinoma, Hereditary papillary renal cell carcinoma, Kidney cancer, Renal cell carcinoma, Tuberous sclerosis complex, von Hippel-Lindau disease",
author = "Carlo, {Maria I.} and Hakimi, {A. Ari} and Stewart, {Grant D.} and Gennady Bratslavsky and Brugarolas, {James B} and Chen, {Ying Bei} and Linehan, {W. Marston} and Maher, {Eamonn R.} and Merino, {Maria J.} and Kenneth Offit and Reuter, {Victor E.} and B. Shuch and Coleman, {Jonathan A.}",
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T2 - Implications of New Syndromes and Molecular Insights

AU - Carlo, Maria I.

AU - Hakimi, A. Ari

AU - Stewart, Grant D.

AU - Bratslavsky, Gennady

AU - Brugarolas, James B

AU - Chen, Ying Bei

AU - Linehan, W. Marston

AU - Maher, Eamonn R.

AU - Merino, Maria J.

AU - Offit, Kenneth

AU - Reuter, Victor E.

AU - Shuch, B.

AU - Coleman, Jonathan A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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. 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.

AB - 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. 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.

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KW - Hereditary leiomyomatosis renal cell carcinoma

KW - Hereditary papillary renal cell carcinoma

KW - Kidney cancer

KW - Renal cell carcinoma

KW - Tuberous sclerosis complex

KW - von Hippel-Lindau disease

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