‘Sex’ in the cancer cell

The development of better tools for diagnosis and more accurate prognosis of cancer includes the search for biomarkers; molecules whose presence, absence or change in quantity or structure is associated with a particular tumour or prognosis/therapeutic outcome. While biomarkers need not be functionally relevant, if their expression influences cell transformation or cancer cell survival, then they could also provide new targets for therapeutic drugs. In recent years attention has been applied to a group of proteins known as cancer testis antigens (CT antigens) [1]. These proteins are products of genes whose expression was originally thought normally to be confined to the testis, yet they are expressed in tumour cells. CT genes are bound to serve a wide array of roles in the testes, which have many highly differentiated cell types and, uniquely, the specialised role of bearing a germline with cells passing through meiosis. Early on, autologous typing of patient antibodies and T-cells demonstrated CT gene expression in tumours, the first example being MAGEA1 in melanoma [1]. Later serological screening of cDNA expression libraries identified further CT antigens including the meiosis specific synaptonemal complex protein 1 (SCP1) in malignant gliomas, breast, renal cell, and ovarian cancer [1]. More recently high throughput technologies have gradually increased the number of apparent CT antigens/genes [1,2]. CT gene expression has been used as a prognostic/stratification tool to identify aggressive metastasis prone lung cancer [3] and chemo-resistance [4]. But wider analysis of gene expression suggests that activity of many CT is not wholly confined to the testis. Some CT genes are expressed in the central nervous system, and others are expressed in a range of normal tissues (see [5]). So, the CT label has been unfortunately applied as misnomer to some antigens/genes, and the generic group is probably not suitable as biomarkers. But, is there a subset of so-called CT genes that really are normally testis specific? Following the discovery that ~25% of Drosophila genes misregulated during malignant brain growth are required in the germ line [6], Feichtinger, et al reasoned that the germline subset of testis expressing genes might be more reliably silent in normal somatic cells [5]. They termed these meiotic cancer testis (meiCT) genes. The functional classification of meiCTs is cautious, as it results from examining gene expression in isolated mouse meiotic cells. Mammalian meiotic function was not demonstrated for all genes, and there could have been non-meiotic cell contamination. Indeed, they …