FaCD Online Syndrome Fact Sheet

Last updated: 31 Mar 2008

Name: Renal Cell Cancer associated with constitutional translocation of chromosome 3

Mode of Inheritance: AD

OMIM number: 144700  


FHIT, mapped to 3p14.2
TRC8, mapped to 8q24.1

Tumor features

renal cell cancer, clear-cell (Grawitz tumor)

Tumor features (possible)

thyroid cancer, anaplastic
thyroid cancer, papillary
urinary bladder cancer

Non-tumor features

t(1;3)(q32;q13.3) (constitutional)
t(2;3)(q35;q21) (constitutional)
t(3;12)(q13.2;q24.1) (constitutional)
t(3;6)(p13;q24.1) (constitutional)
t(3;6)(q22;q16.1) (constitutional)
t(3;8)(p14.2;q24.1) (constitutional)


Several authors [1,2,10,11] reported a familial translocation between chromosomes 3 and 8 segregating with early onset (range 37-65 years), bilateral, renal cell cancer. One of the female patients also developed multifocal papillary and undifferentiated thyroid cancer. Gemmill et al.[3] demonstrated that the translocation caused the fusion of the FHIT and TRC8 gene, of which the latter probably is the critical gene.

Kovacs et al.[4] reported a family with a constitutional translocation of chromosomes 3 and 6. The oldest family member known to carry the translocation was diagnosed at the age of 53 years with bilateral multiple non-papillary renal cell cancer. The other relatives were still young and may possibly develop renal cell cancer at an older age. Van den Berg et al.[5] demonstrated that the breakpoint in 3p was different from that in the 3;8 translocation associated with renal cell cancer. Koolen et al.[6] reported a familial translocation between 2q and 3q, which segregated with 4 cases of renal cancer (3 of them proven clear cell type, ages at diagnosis 40, 53, 54 and 68 years) and one case of squamous cell bladder cancer (diagnosed at the age of 66 years). Kanayama [12] reported four cases of late onset clear cell renal cell carcinoma associated with a familial (1;3) translocation. Van Kessel et al.[7] looked at 10 families with a familial chromosome 3 translocation and found 4 patients with renal cell cancer out of the total 57 chromosome 3 translocation carriers (only those older than 25 years were included). The authors concluded that carriers of (familial) reciprocal chromosome 3 translocations may be at an substantially increased risk to develop renal cell cancer, especially when translocation breakpoints are located near the centromere.

Bodmer et al.[8] analyzed the renal tumors from 3 of the patients and found a loss of the der(3) chromosome in all of them. The authors interpreted this as support for the theory of Kovacs and Hoene[9] who reported the loss of der(3) in the renal cell carcinoma of a 50-year-old man with a (possibly de novo) t(3;12)(q13.2;q24.1) and therefore postulated that reciprocal translocations could at the somatic level lead to non-disjunctional loss of the der(3) chromosome harboring tumor suppressor genes (incl. VHL). A somatic mutation of the remaining copies of one or more of these genes would then result in the development of renal tumors.
Several more observations have been added to the list[10-13].


[1] Cohen AJ, Li FP, Berg S, Marchetto DJ, Tsai S, Jacobs SC, Brown RS. Hereditary renal-cell carcinoma associated with a chromosomal translocation. N Engl J Med 1979; 301(11):592-595.
[2] Li FP, Decker HJH, Zbar B, Stanton JVP, Kovacs G, Seizinger BR, Aburratani H, Sandberg AA, Berg S, Hosoe S, Brown RS. Clinical and genetic studies of renal cell carcinomas in a family with a constitutional chromosome 3;8 translocation. Ann Intern Med 1993; 118(2):106-111.
[3] Gemmill RM, West JD, Boldog F, Tanaka N, Robinson LJ, Smith DI, Li F, Drabkin HA. The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8. Proc Natl Acad Sci U S A 95[16], 9572-9577. 1998.
[4] Kovacs G, Brusa P, de Riese W. Tissue-specific expression of a constitutional 3;6 translocation: development of multiple bilateral renal-cell carcinoma. Int J Cancer 1989; 43:422-427.
[5] Van den Berg A, Van der Veen AY, Hulsbeek MMF, Kovacs G, Gemmill RM, Drabkin HA, Buys CHCM. Defining the position of the breakpoint of the constitutional t(3;6) occurring in a family with renal cell carcinoma. Gene Chrom Cancer 1995; 12:224-228.
[6] Koolen MI, van der Meyden PM, Bodmer D, Eleveld M, van der Looij E, Brunner H, Smits A, van den Berg E, Smeets D, Geurts van Kessel A. A familial case of renal cell carcinoma and a t(2;3) chromosome translocation. Kidney Int 53[2], 273-275. 1998.
[7] Geurts van Kessel A, Wijnhoven H, Bodmer D, Eleveld M, Kiemeney L, Mulders P, Weterman M, Ligtenberg M, Smeets D, Smits A. Renal cell cancer: chromosome 3 translocations as risk factors. J Natl Cancer Inst 1999; 91(13):1159-1160.
[8] Bodmer D, Eleveld MJ, Ligtenberg MJL, Weterman MAJ, Janssen BAP, Smeets DFCM, de Wit PEJ, Van den Berg A, van den Berg E, Koolen MI, Geurts van Kessel A. An alternative route for multistep tumorigenesis in a novel case of hereditary renal cell cancer and a t(2;3)(q35;q21) chromosome translocation. Am J Hum Genet 62[6], 1475-1483. 1998.
[9] Kovacs G, Hoene E. Loss of der(3) in renal carcinoma cells of a patient with constitutional t(3;12). Hum Genet 1988; 78:148-150.
[10] Meléndez B, Rodríguez-Perales S, Martínez-Delgado B, Otero I, Robledo M, Martínez-Ramírez A, Ruiz-Llorente S, Urioste M, Cigudosa JC, Benítez J. Molecular study of a new family with hereditary renal cell carcinoma and a translocation t(3;8)(p13;q24.1). Human genetics 2003; 112(2):178-85.
[11] Poland KS, Azim M, Folsom M, Goldfarb R, Naeem R, Korch C, Drabkin HA, Gemmill RM, Plon SE. A constitutional balanced t(3;8)(p14;q24.1) translocation results in disruption of the TRC8 gene and predisposition to clear cell renal cell carcinoma. Genes, chromosomes & cancer 2007; 46(9):805-12.
[12] Kanayama H, Lui WO, Takahashi M, Naroda T, Kedra D, Wong FK, Kuroki Y, Nakahori Y, Larsson C, Kagawa S, Teh BT. Association of a novel constitutional translocation t(1q;3q) with familial renal cell carcinoma. Journal of medical genetics 2001; 38(3):165-70.
[13] Foster RE, Abdulrahman M, Morris MR, Prigmore E, Gribble S, Ng B, Gentle D, Ready S, Weston PM, Wiesener MS, Kishida T, Yao M, Davison V, Barbero JL, Chu C, Carter NP, Latif F, Maher ER. Characterization of a 3;6 translocation associated with renal cell carcinoma. Genes, chromosomes & cancer 2007; 46(4):311-7.