SUO 2018: Hereditary Kidney Cancer and Genetic Testing – UroToday

SUO 2018: Hereditary Kidney Cancer and Genetic Testing – UroToday

Phoenix, Arizona ( Dr. Maria Carlo gave a short overview of the extra frequent and fewer frequent renal hereditary most cancers syndromes and a few tips on when ought to sufferers be referred for genetic testing. Determine 1 demonstrates the prevalence of germline mutations in renal cell carcinoma (RCC) instances within the most cancers genome atlas (TCGA). A complete of 6%, 9% and 6% of all clear-cell, papillary, and chromophobe RCC instances, respectively are a germline mutation. Probably the most often mutated genes are VHL and BAP1 in clear cell, FH and MET in papillary, and CHEK2, NF1, MSH6 in chromophobe.

Determine 1 – Prevalence of germline mutations in renal cell carcinoma instances within the Most cancers Genome Atlas:

The really useful referral indications for genetic evaluation embrace:

  1. Clear cell RCC with both:
    • Age < 50
    • Bilateral or multifocal tumors
    • >=1 shut relative with clear cell RCC
  2. Papillary sort 1 or 2
  3. Gathering duct histology
  4. Tubulopapillary histology
  5. Birt-Hogg Dube associated histology (Chromophobe, oncocytoma, oncocytic hybrid)
  6. RCC with 2 further options of Cowden syndrome (PTEN germline mutations)
  7. Angiomyolipomas and one further characteristic of tuberous sclerosis:

Subsequent, Dr, Carlo mentioned the hereditary Leiomyomatosis and RCC (HLRCC) syndrome, which is related to germline mutations in FH, encoding for an enzyme within the Krebs cycle. There may be additionally an related 10-20% lifetime threat of RCC (papillary sort 2/HLRCC-associated RCC). It’s generally related to uterine fibroids (practically 100% penetrance), and pores and skin leiomyomas. The related small renal tumors can metastasize and have a tendency to have a poor prognosis. HLRCC is frequent in sufferers with superior non-clear cell RCC, and the pathology just isn’t at all times informative. The mix of Bevacizumab and erlotinib or everolimus has been assessed in HLRCC-associated RCC. Bevacizumab+erlotinib reveal an general response fee of 65%.

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BAP1-hereditary most cancers syndrome is related to germline mutations in BAP1, which encodes a deubiquitinase. It will increase the danger of uveal and cutaneous melanoma, renal cell carcinoma, pleural and peritoneal mesothelioma, and presumably different cancers.

Lastly, Dr. Carlo talked about the hereditary paraganglioma-pheochromocytoma syndrome, which is related to germline mutations in SDHA, DHB, DHC, SDHD, and SDHAF. These encode for a Krebs cycle enzyme.  On this syndrome, there’s an elevated threat of pheochromocytoma, GIST tumors and SDH-deficient RCC. The very best threat of RCC is in carriers of SDHB. Sufferers needs to be referred for genetic evaluation if they’ve:

  • Pheochromocytoma or paraganglioma
  • RCC with a household historical past of pheochromocytoma or paraganglioma
  • SDH-deficient RCC

Introduced by: Maria Carlo, MD, Medical Oncologist, Memorial Sloan Kettering Most cancers Middle, New-York, NY

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow, SUO, College of Toronto, Princess Margaret Most cancers Centre, @GoldbergHanan, on the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona

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