Genetic profile of bone metastases in renal cell carcinoma

Abstract

Objective: The aim of this study was to define specific genetic alterations which are common in bone metastases in renal cancer patients.

Methods: Tumor DNA from 31 metastases and 13 related primary tumors was extracted from paraffin embedded tissue sections. DOP-PCR was performed to amplify the whole DNA. After labelling by PCR, CGH was performed according to standard protocols.

Results: The mean number of aberrations per metastasis was 6.3 (1-13). Losses of chromosomes 3p (76%), 6 (20%), 8p (20%), 9 (34%), 14q (27%) and 18 (20%) as well as gains of chromosomes 5 (45%), 8q (34%) and 17 (27%) were detected frequently. Thirteen related primary tumors were also investigated. In 7 cases, at least one identical alteration was found in both primary tumor and metastases. In these cases, the number of alterations was mostly higher in primary tumors than in metastases without statistical significance. However, in general, the frequency of alterations was higher in metastases.

Conclusions: Bone metastases from renal cell carcinoma are characterized by typical genetic alterations. Changes leading to metastasizing happen early in tumor pathogenesis. However, further accumulation of genetic changes occurs in metastases leading to a more complex genetic pattern which might be necessary for progression to clinically relevant metastases.