FaCD Online Syndrome Fact Sheet

Last updated: 27 Jun 2012

Name: Hereditary Papillary Renal Carcinoma (type 1)

Synonym: HPRC, Hereditary Papillary Renal Cell Cancer

Mode of Inheritance: AD

Genes

MET, mapped to 7q31
MITF, mapped to 3p14-p13

Tumor features

renal cell cancer, papillary type 1
renal papillary adenoma

Tumor features (possible)

gastric cancer

Comment

This disorder is clinically defined by the presence of multiple papillary, type 1, renal cancers[1] in at least 2 successive generations[2-4]. Papillary adenomas are found as well. Histological cancer subtype is papillary renal carcinoma type 1 (chromophil basophilic)[5]. These tumors are often missed by ultrasound screening and enhance poorly on CT[6].
The chance of finding germline MET mutations in patients with papillary renal cell cancer in the absence of features suggestive of inherited disease, like a positive family history or early age at diagnosis, appears to be small[7,10].

A germline missense MET mutations was also observed in two patients with gastric cancer, one with diffuse and the other with intestinal type[8,9].

Berlotto et al[11] investigated patients with melanoma and/or renal cancer. They identified the E318K MITF variant as a gain-of-function mutation in this group and showed that carriers had a higher than fivefold increased risk of developing melanoma, RCC (clear cell or papillary type 1) or both cancers.

References

[1] Ornstein DK, Lubensky IA, Venzon D, Zbar B, Linehan WM, Walther MM. Prevalence of microscopic tumors in normal appearing renal parenchyma of patients with hereditary papillary renal cancer. J Urol 2000; 163(2):431-433.
[2] Zbar B, Tory K, Merino M, Schmidt L, Glenn G, Choyke P, McClellan MW, Lerman M, Linehan WM. Hereditary papillary renal cell carcinoma. J Urol 1994; 151:561-566.
[3] Zbar B, Glenn G, Lubensky I, Choyke P, Walther MM, Magnusson G, Bergerheim USR, Pettersson S, Amin M, Hurley K, Linehan WM. Hereditary papillary renal cell carcinoma: Clinical studies in 10 families. J Urol 1995; 153:907-912.
[4] Zbar B, Glenn G, Lubensky I, Choyke P, Walther MM, Magnusson G, Bergerheim USR, Pettersson S, Amin M, Hurley K, Linehan WM. Letters to the editor: Hereditary papillary renal cell carcinoma: clinical studies in 10 families. J Urol 1996; 156:1781.
[5] Schmidt L, Lubensky I, Linehan WM, Zbar B. Hereditary papillary renal carcinoma: pathology and pathogenesis. Contrib Nephrol 1999; 128: 11-27:11-27.
[6] Choyke PL, Walther MM, Glenn GM, Wagner JR, Venzon DJ, Lubensky IA, Zbar B, Linehan WM. Imaging features of hereditary papillary renal cancers. J Comput Assist Tomogr 21[5], 737-741. 1997.
[7] Lindor NM, Dechet CB, Greene MH, Jenkins RB, Zincke MT, Weaver AL, Wilson M, Zincke H, Liu W. Papillary renal cell carcinoma: analysis of germline mutations in the MET proto-oncogene in a clinic-based population. Genetic testing 2001; 5(2):101-6.
[8] Kim IJ, Park JH, Kang HC, Shin Y, Lim SB, Ku JL, Yang HK, Lee KU, Park JG. A novel germline mutation in the MET extracellular domain in a Korean patient with the diffuse type of familial gastric cancer. J Med Genet. 2003 Aug;40(8):e97
[9] Lee JH, Han SU, Cho H, Jennings B, Gerrard B, Dean M, Schmidt L, Zbar B, Vande Woude GF. A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene 2000; 19(43):4947-53.
[10] Salvi A, Marchina E, Benetti A, Grigolato P, De Petro G, Barlati S. Germline and somatic c-met mutations in multifocal/bilateral and sporadic papillary renal carcinomas of selected patients. Int J Oncol. 2008 Aug;33(2):271-6.
[11] Bertolotto C et al. A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma. Nature 2011; 480:94-8.