Seminomas Liked to Gene Overexpression

A study has shown that overexpression of a gene called hiwi, a member of the piwi family of genes, is indicative of germ cell testicular tumors, called seminomas. The piwi genes are highly conserved during evolution and play essential roles in stem cell self-renewal, gametogenesis, and RNA interference in diverse organisms. The findings were published in the June 6, 2002, issue of Oncogene.

Researchers from Duke University Medical Center (Durham, NC, USA) found that in seminomas, the reproductive stem cells expressed the hiwi gene at an unusually high rate. The gene activity in the cancer samples was up to 16 times higher than that of a healthy patient. Although the patient sample size was small (12 of 19 patients, or 63%, expressed the hiwi gene in abnormally high levels), the findings were considered to be statistically significant. The hiwi gene was mapped to a region on the long arm of chromosome 12, previously linked to the development of seminomas and other testicular cancers.

"There are several other genes known to be associated with testicular cancer at very low frequencies (10 % or lower). This is the first study to establish a high level correlation between a gene and seminoma,” said Dr. Haifan Lin. Dr. Lin believes that an underactive or nonactive hiwi gene can cause sterility in men because the same gene in drosophila and mice, called piwi and miwi, respectively, are known to cause sterility.

Overexpression of the hiwi gene was not detected in a different type of testicular cancer called nonseminoma. Nor was overexpression detected in spermatocytic seminomas, which are benign testicular tumors that originate from germ cells. Also, hyperactivity of the hiwi gene was not found in testicular tumors caused by overproliferation of somatic cells in the testes.

The investigators hope that the results of this study could lead to genetic testing to predict the risk for developing seminoma. They could also lead to new treatments in affected individuals by genetically reprogramming the reproductive cells to multiply at safe levels. There is also the possibility of developing stem cell therapy to cure infertility due to defects in hiwi-related regulatory processes.





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