FREQUENT LOSS OF HETEROZYGOSITY AT 11P LOCI IN TESTICULAR CANCER

Deletions of segments of chromosome 11 have been found to be involved in several human tumors. Specific deletion of chromosomal band 11p13 has been associated with Wilms' tumors and gonadoblastomas. We performed a deletion analysis of 11p using 6 polymorphic probes and DNA from 30 testicular malignancies with corresponding normal DNA in 19 patients. A cDNA probe (WT 33) was used to evaluate the Wilms' tumor suppressor gene (WT1) for loss by gene dosage analysis. Results using the polymorphic probes revealed loss of heterozygosity on 11p in 59% of informative samples, while use of the WT1 probe revealed loss of hemizygosity in 27% of the samples. Northern blot analysis of WT1 was performed on mRNA from 3 normal and 1 malignant testis, as well as from 4 testicular cancer cell lines (TERA 1, TERA 2, HTE and HTH). Northern blot analysis of the normal testes revealed the presence of the expected 3.2 and 2.7 kb transcripts. The TERA 1, TERA 2 and HTH cell lines were found to express only the 3.2 kb transcript and at levels only 3.3%, 29% and 2.8% of normal testes. The HTE cell line did not express either of the normal transcripts. Our results reveal considerable allelic loss at 11p13 and 11p15, suggesting that these loci may harbor one or more tumor suppressor genes important in the development of testicular cancer.