Translocation Renal Cell Carcinoma

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Synonyms

tRCC,

Overview

Xp11 translocation renal cell carcinomas (RCCs) are a distinctive subtype of RCC characterized by chromosomal translocations with breakpoints involving the TFE3 transcription factor gene, which maps to the Xp11.2 locus. The result is a fusion of the TFE3 transcription factor gene with one of multiple reported genes including ASPSCR1 ( ASPL), PRCC, NonO (p54nrb), SFPQ (PSF), and CLTC (Table 1). The three most common Xp11 translocation RCCs are those bearing the t(X;1)(p11.2;q21) which fuses the PRCC and TFE3 genes, the t(X;17)(p11.2;q25) which fuses the ASPSCR1 and TFE3 genes , and the t(X;1)(p11.2;p34) which fuses the SFPQ (PSF) and TFE3 genes. The ASPSCR1-TFE3 gene fusion is the same gene fusion found in alveolar soft part sarcoma (ASPS), a rare pediatric neoplasm of uncertain histogenesis. However, the translocation in Xp11 translocation RCC is balanced, which may contribute to the differences seen at the clinical and histopathologic levels between Xp11 translocation RCC and ASPS. Other reported but rare translocations are the inv (X)(p11.2;q12) which fuses the NonO (p54nrb) and TFE3 genes; the t(X;17)(p11.2;q23) which fuses the CLTC and TFE3 genes5 , and the t(X;3)(p11.2;q23)6 which fused the PARP14 and TFE3 genes. Variant translocations with no known fusion partner include t(X;10)(11.2;q23).

Xp11 translocation RCC were first recognized in children. Although RCC accounts for less than 5% of renal neoplasms in children, Xp11 translocation RCCs constitute a significant percentage of these cases. Approximately 40% of pediatric RCC have been classified as Xp11 translocation RCC, with a range from 20% to 75% of pediatric RCC cases among different series. The higher frequencies have generally come from single institution series, which may be less biased than multi-institution, tumor-repository based series.

The frequency of Xp11 translocation RCC in adults may be underestimated, perhaps due to morphological overlap with more common adult RCC subtypes, such a conventional clear cell RCC and papillary RCC. The frequency ranges from 1-4% in different studies. While Xp11 translocation RCC is therefore on a percentage basis rare in adults, RCC is overall much more common in adults than in children. If there are approximately 30,000 new cases of RCCs in adults each year, 4.2 % of 30,000 cases would total 1,260 adult Xp11 translocation RCC per year. In contrast, 40% of the 25 pediatric RCC in the United States would total 10 pediatric Xp11 translocation RCC per year. Thus, adult Xp11 translocation RCC may outnumber pediatric Xp11 translocation RCC by orders of magnitude due to the much higher incidence of RCC in the adult population.

Prior exposure to cytotoxic chemotherapy is currently the only known risk factor for development of Xp11 translocation RCC: up to 15% of patients with these tumors had a history of prior chemotherapy exposure. Indications for chemotherapy have included Wilms tumor, Ewing sarcoma, systemic lupus erythematosus (SLE), acute leukemia, and bone marrow transplant. The post-chemotherapy interval ranged from 4-13 years, though more recent studies have documented occurrence of Xp11 translocation RCC within 2 years of chemotherapy. All reported patients received either a DNA topoisomerase II inhibitor and/or an alkylating agent. Although they have differing mechanisms of action, both cytotoxic agents break DNA, which may initiate repair or recombination mechanisms that permit a chromosome translocation to occur.

Causes

Prior exposure to cytotoxic chemotherapy is currently the only known risk factor for development of Xp11 translocation RCC: up to 15% of patients with these tumors had a history of prior chemotherapy exposure. Indications for chemotherapy have included Wilms tumor, Ewing sarcoma, systemic lupus erythematosus (SLE), acute leukemia, and bone marrow transplant. The post-chemotherapy interval ranged from 4-13 years, though more recent studies have documented occurrence of Xp11 translocation RCC within 2 years of chemotherapy. All reported patients received either a DNA topoisomerase II inhibitor and/or an alkylating agent. Although they have differing mechanisms of action, both cytotoxic agents break DNA, which may initiate repair or recombination mechanisms that permit a chromosome translocation to occur.

Prognosis

The estimate of how a disease will affect you long-term is called prognosis. Every person is different and prognosis will depend on many factors, such as

  • Where the tumor is in your body
  • If the cancer has spread to other parts of your body
  • How much of the tumor was taken out during surgery

If you want information on your prognosis, it is important to talk to your doctor. NCI also has resources to help you understand cancer prognosis.

Doctors estimate translocation renal cell carcinoma survival rates by how groups of people with TRCC have done in the past. Because there are so few patients, these rates may not be very accurate.

Patients diagnosed in childhood usually have a better prognosis than patients diagnosed in adulthood. Translocation renal cell carcinoma can spread to other parts of the body many years after it is diagnosed, so it is important that patients continue to visit their doctor after treatment.

Treatment

Treatment options for patients depend on the how the cancer is growing and whether the cancer has spread to other parts of the body, called metastasis.

Surgery: For patients with less advanced stages of TRCC, surgery to remove the tumor is a treatment option.

Targeted therapy: Patients with more advanced TRCC are given specific types of drugs to kill the cancer cells.