The Gametogenic Cancer Connection

In 1902, James Beard suggested the hypothesis that: “Cancer is derived from vagrant primary germ-cells, which, instead of forming a more or less complete embryo or embryoma, skip this and give rise to a larva or phorozoon of indefinite and unrestricted power of growth” (The Lancet). While his theory was quite a bit out of left field, mounting evidence now suggests that cancer cells aberrantly induce the expression of genes that are otherwise primarily expressed in the gametogenic cells (sperm/oocytes) or trophoblasts.  

The initial discovery that cancer cells abnormally express gametogenic genes was made by cancer immunologist Thierry Boon.  In 1991, the Boon lab identified tumor antigen MZ2-E, which was encoded by the gene, MAGE1. The Boon group discovered that MAGE1 was only expressed in testicular germ cells, but frequently abnormally expressed in cancer cells.  Subsequently, additional tumor antigens encoded by testicular germ cells were identified including: BAGE and GAGE, both of which were members of multi-gene families exhibiting this surprising expression pattern. Lloyd Old’s group then discovered NY-ESO-1, encoded by the CTAG1B gene, which exhibited high immunogenicity, eliciting both antibody and T-cell responses in cancer patients. By 2004, ~40 cancer testis antigen families had been identified. In 2009, using a genome-wide approach, Lloyd Old’s group established classified  ~200 genes as cancer testes antigens based on the biased expression to gametes and cancer. Notably, this approach revealed low expression of a cohort of these genes in additional somatic tissues, most prominently brain. A few others exhibit enrichment in one or two normal tissues. More recently, the availability of single-cell sequencing data, TCGA and normal expression data sets led Charles de Smet’s group to redefine genes with very tight gamete/trophoblast and tumor expression patterns as well as establish a search tool to analyze any gene (see paper here). These genes could represent targets for immunotherapy, direct targeting with small molecule inhibitors and new tumor biology.

Probably the most controversial area in this field is how to refer to these group of genes and their encoded proteins. They may be referred to as Cancer Testis Genes (CT-Genes, CTP-Genes (p=preferential), Cancer Testis Antigens (CT-Antigens, CTAs), or Cancer-germline genes (CG-Genes). All of these names are widely accepted in reference to a gene whose expression is low/absent in somatic cells but expressed in gametes, trophoblasts and/or placenta.

This site is dedicated to bringing the many individuals interested in these unique proteins together to exchange ideas, connect and continue to grow this field. There are a number of open questions to address (see the Topics page) and the hope is we can begin to close these knowledge gap through a more interconnected community.

If you have suggestions or additions for this site, please email them to: ctantigens@gmail.com.