To facilitate the development of molecular based diagnostic tools and targeted therapies for this aggressive kidney cancer, we generated a translocation RCC mouse model, in which the <i>PRCC-TFE3</i> transgene is expressed specifically in kidneys leading to the development of RCC with characteristic histology.
Renal cell carcinomas (RCCs) with Xp11 translocation (Xp11 RCC) constitute a distinctive molecular subtype characterized by chromosomal translocations involving the Xp11.2 locus, resulting in gene fusions between the TFE3 transcription factor with a second gene (usually ASPSCR1, PRCC, NONO, or SFPQ).
We corroborate prior data showing that the PRCC-TFE3 RCCs are the only known Xp11 translocation RCC molecular subtype that are consistently cathepsin K positive.
The most common translocations documented in TFE3 RCCs are t(X;1) (p11.2;q21) and t(X;17) (p11.2;q25) which leads to fusion of TFE3 gene on Xp11.2 with PRCC or ASPL respectively.
Recently, a unique translocation between the X chromosome and chromosome 1 or t(X;1) has been described in several reports of renal cell carcinomas (RCCs) diagnosed in children and adolescents that results in PRCC-TFE3 gene fusion.
The endothelin axis was expressed differently in the two main subtypes of RCC and appeared to match macroscopic features commonly observed in these tumors (i.e., high expression of PPET-1 in hypervascular ccRCC contrasted against low PPET-1 and ET(A) expression in hypovascular PRCC).
Previously, we demonstrated that in t(X;1)(p11;q21)-positive renal cell carcinomas (RCCs), the TFE3 gene on the X chromosome is disrupted and fused to the PRCC gene on chromosome 1.
Both fusion genes are expressed in t(X;1)-positive renal cell carcinomas and contain major parts of the coding regions of the parental transcription factor PRCC and TFE3 genes, respectively.
Germline mutations in the tyrosine-kinase domain of the MET proto-oncogene were found in patients suffering from the hereditary predisposition to develop multiple papillary renal-cell carcinomas (hereditary PRCC, HPRCC).