Cancer/testis antigens and gametogenesis: a review and "brain-storming" session

Abstract

Genes expressed both in normal testis and in malignancies (Cancer/ Testis associated genes - CTA) have become the most extensively studied antigen group in the field of tumour immunology. Despite this, many fundamentally important questions remain unanswered: what is the connection between germ-cell specific genes and tumours? Is the expression of these genes yet another proof for the importance of genome destabilisation in the process of tumorigenesis?, or maybe activation of these genes is not quite random but instead related to some programme giving tumours a survival advantage?This review collates most of the recent information available about CTAs expression, function, and regulation. The data suggests a programme related to ontogenesis, mostly to gametogenesis. In the "brain-storming" part, facts in conflict with the hypothesis of random CTA gene activation are discussed. We propose a programme borrowed from organisms phylogenetically much older than humans, which existed before the differentiation of sexes. It is a programme that has served as a life cycle with prominent ploidy changes, and from which, as we know, the germ-cell ploidy cycle - meiosis - has evolved. Further work may show whether this hypothesis can lead to a novel anti-tumour strategy.

Figure 1

Expression of CTAs during male germ cell development. References for Fig. 1: [25] [27] [28] [37] [40] [42] [53] [92] [93] [94] [95] [96]

Figure 2

Oncogene expression during spermatogenesis (mainly in mice). From [70].

Figure 3

Reductional mitotic divisions generating low ploidy cells from one large polyploid cell. Non-treated Burkitt's lymphoma cell line, DNA staining with Toluidine-blue. × 2,500.