Changes in telomere lengths in renal cell carcinomas.

Telomeres, the extreme ends of chromosomes, play an important role in chromosome structure and function. The shortening of telomeres is one of the supposed mechanisms of cellular aging and death. Because of end replication problems the length of telomeres decreases with every cell cycle. This may lead to chromosome instability and additional genetic alterations possibly responsible of significant tumor development. In many cancer cells the length of telomeres depends on a balance between the loss of telomeric repeats, at each replication cycle, and the telomere lengthening, by the enzyme telomerase, which is repressed in most normal somatic cells. Many tumor cells demonstrate shortened telomeres in comparison to the corresponding normal tissue. In some types of human cancers the reduction of telomeric repeats was correlated with increasing disease severity. We analyzed Southern blots of HINF1-digested DNA of a large number of renal cell carcinomas (RCC) including different tumor areas, secondary tumors and metastases (76 cases with 142 tumor samples) for changes in the length of telomeric repeats using the oligonucleotide probe (TTAGGG)3 and found telomere shortening in 54%, suggesting that a reduction of the telomeric repeat length is not a general characteristic in RCC. Intratumor heterogeneity was demonstrated in seven cases. But also two RCC, with elongated telomeres in the tumor tissue, were observed. Shortened telomeres do not seem to be associated with advanced stages of tumor development or specific histopathological subtypes of RCC.