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

Genes

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)

Comment

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].

References