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Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas

Abstract

The piwi family genes are highly conserved during evolution and play essential roles in stem cell self-renewal, gametogenesis, and RNA interference in diverse organisms ranging from Drosophila melanogaster and C. elegans to Arabidopsis. Here we report the molecular characterization of hiwi, a human member of the piwi gene family. hiwi maps to the long arm of chromosome 12, band 12q24.33, a genomic region that displays genetic linkage to the development of testicular germ cell tumors of adolescents and adults (TGCTs), i.e., seminomas and nonseminomas. In addition, gain of this chromosomal region has been found in some TGCTs. hiwi encodes a 3.6 kb mRNA that is expressed abundantly in the adult testis. It encodes a highly basic 861-amino-acid protein that shares significant homology throughout its entire length with other members of the PIWI family proteins in Drosophila, C. elegans and mammals. In normal human testes, hiwi is specifically expressed in germline cells, with its expression detectable in spermatocytes and round spermatids during spermatogenesis. No expresssion was observed in testicular tumors of somatic origin, such as Sertoli cell and Leydig cell tumors. Enhanced expression was found in 12 out of 19 sampled testicular seminomas–tumors originating from embryonic germ cells with retention of germ cell phenotype. In contrast, no enhanced expression was detected in 10 nonseminomas–testicular tumors that originate from the same precursor cells as seminomas yet have lost their germ cell characteristics. Finally, no enhanced expression was detected in four spermatocytic seminomas–testicular tumors that most likely originate from germ cells capable of partial meiosis. Thus, hiwi is specifically expressed in both normal and malignant spermatogenic cells in a maturation stage-dependent pattern, in which it might function in germ cell proliferation.

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Acknowledgements

We thank Ms H Abushama for mapping the hiwi gene, Ms Jennifer Powers and Dr Sandra Bigner for providing human testicular samples, and Lin lab members for comments on the manuscript. Ad Gillis is thanked for his technical support. This work is supported by grants from NIH (HD33760, HD42012) and the David and Lucile Packard Foundation to Haifan Lin and by the Dutch Cancer Society (KWF) to Anne-Marie Zeeman (grant DDHK 99-1968) and Leendert HJ Looijenga.

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Correspondence to Haifan Lin.

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Qiao, D., Zeeman, AM., Deng, W. et al. Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene 21, 3988–3999 (2002). https://doi.org/10.1038/sj.onc.1205505

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