Hereditary renal cell carcinoma

Hereditary renal cell carcinoma is relatively uncommon.

General

The classics - which are all autosomal dominant:

1. Von Hippel-Lindau syndrome.
   • VHL gene mutation.
   • Clear cell RCC.
2. Hereditary clear cell renal cell carcinoma.
   • VHL gene mutation.
3. Hereditary papillary renal cell carcinoma.
   • MET proto-oncogene mutation.
   • PaRCC type 1.
4. Hereditary leiomyomatosis and renal cell cancer:
   • FH (fumarate hydratase) gene mutation.
   • PaRCC type 2.
   • Benign leiomyomas skin/uterus.
   • Uterine leiomyosarcoma.
5. Birt–Hogg–Dubé syndrome:
   • FLCN (folliculin) gene mutation.
   • Skin lesions (fibrofolliculoma, trichodiscoma, acrochordon).
   • ChRCC most common, other types seen (e.g. oncocytoma).
   • Variable penetrance (autosomal dominant).

Others:

• Hereditary papillary carcinoma (TFE3 related translocations).

Notes:

• A total of ten hereditary renal cancer syndromes have been described. In eight of the ten the gene is known.

Molecular

Recurrent molecular changes in RCC:

• Clear cell RCC:
  • Loss of 3p - contains the VHL gene.
• Papillary RCC:
  • Sporadic:
    • Trisomy 7, 16, 17.
    • Loss of Y.
  • Familial:
    • Trisomy 7 - contains MET gene.

See also

• Kidney tumours.