Eble JN, Sauter G., Epstein JI, Sesterhenn IA - iarc

Familial renal cell carcinoma
M.J. Merino
D.M. Eccles
W.M. Linehan
F. Algaba
B. Zbar
G. Kovacs
P. Kleihues
A. Geurts van Kessel
M. Kiuru
V. Launonen
R. Herva
L.A. Aaltonen
H.P.H. Neumann
C.P. Pavlovich
The kidney is affected in a variety of
inherited cancer syndromes. For most of
them, the oncogene / tumour suppressor
gene involved and the respective
germline mutations have been identified,
making it possible to confirm the clinical
diagnosis syndrome, and to identify
asymptomatic gene carriers by germline
mutation testing {2510}. Each of the
inherited syndromes predisposes to distinct
types of renal carcinoma. Usually,
affected patients develop bilateral, multiple
renal tumours; regular screening of
mutation carriers for renal and extrarenal
manifestations is considered mandatory.
Von Hippel-Lindau disease (VHL)
Definition
The von Hippel-Lindau (VHL) disease is
inherited through an autosomal dominant
trait and characterized by the development
of capillary haemangioblastomas of
the central nervous system and retina,
clear cell renal carcinoma, phaeochromocytoma,
pancreatic and inner ear
tumours. The syndrome is caused by
germline mutations of the VHL tumour
suppressor gene, located on chromosome
3p25–26. The VHL protein is involved in cell
cycle regulation and angiogenesis.
Approximately 25% of haemangioblastomas
are associated with VHL disease {1883}.
MIM No. 193300 {1679}.
Synonyms and historical annotation
Lindau {1506} described capillary haemangioblastoma,
and also noted its association
with retinal vascular tumours, previously
described by von Hippel {2752}, and
tumours of the visceral organs, including
kidney.
Incidence
Von Hippel-Lindau disease is estimated
Table 1.01
Major inherited tumour syndromes involving the kidney. Modified, from C.P. Pavlovich et al. {2032}
Syndrome Gene Chromosome Kidney Skin Other tissues
Protein
von Hippel-Lindau VHL 3p25 Multiple, bilateral clear-cell - Retinal and CNS haemangioblastopVHL
renal cell carcinoma (CCRCC), mas, phaeochromocytoma, pancrerenal
cysts
atic cysts and neuroendocrine
tumours, endolymphatic sac tumours
of the inner ear, epididymal and
broad ligament cystadenomas
Hereditary papillary c-MET 7q31 Multiple, bilateral papillary - -
renal cancer HGF-R renal cell carcinomas (PRCC)
Type 1
Hereditary leiomyo- FH 1q42-43 Papillary renal cell carcinoma Nodules (leiomyomas) Uterine leiomyomas and
matosis and RCC FH (PRCC), non-Type 1 leiomyosarcomas
Birt-Hogg-Dubé BHD 17p11.2 Multiple chromophobe RCC, Facial fibrofolliculomas Lung cysts, spontaneous
Folliculin conventional RCC, hybrid pneumothorax
oncocytoma, papillary RCC,
oncocytic tumours
Tuberous sclerosis TSC1 9q34 Multiple, bilateral angiomyolipomas, Cutaneous angiofibroma Cardiac rhabdomyomas,
Hamartin lymphangioleiomyomatosis (‘adenoma sebaceum’) adenomatous polyps of the duodenum
TSC2 16p13 peau chagrin, subungual and the small intestine, lung and
Tuberin fibromas kidney cysts, cortical tubers and
subependymal giant cell
astrocytomas (SEGA)
Constitutional Unknown Multiple, bilateral clear-cell - -
chromosome 3
renal cell carcinomas (CCRCC)
translocation
Familial renal cell carcinoma
15