Identification and characterisation of germline-associated genes as potential human cancer biomarkers

Electronic versions

Dogfennau

  • Stephen Sammut

Abstract

It is increasingly apparent that cancer cells exhibit major intraclonal and interclonal heterogeneity that impacts on disease behaviour, response to treatments as well as clinical outcomes for patients. Understanding this diversity is critical to gain insights that ultimately influence treatment decisions in the era of personalised medicine. There is an increasing need to identify unique and relevant diagnostic and prognostic protein biomarkers to allow better stratification. Identification of aberrant gene expression patterns is one way in which additional insights into cancer causation can be discovered and can also inform novel therapeutic targets. In this study we sought to focus on a group of proteins that are predominantly present in the germline but not in somatic cells. It is now well established that cancer cells exhibit aberrant expression of germline factors. Cancer testis antigens (CTAs) are one such family of proteins that exhibit increased presence in a variety of cancers and are also potentially immunogenic. As meiotic cell division is restricted to germline cells such as the testis, we hypothesised that identification and characterisation of genes that govern this process may yield additional clinically useful biomarkers that are also relevant to disease biology and behaviour. With the aid of a pre-existing computational and bioinformatics approach, we first identified a subset of genes, some of which were likely to be involved in meiosis, and interrogated normal and cancerous cells to ascertain their expression pattern. This allowed us to identify a distinct cohort of candidate genes that appeared to be predominantly expressed in the germline and cancer. Immunohistochemistry using normal and (predominantly colorectal) cancer tissues was performed for further evaluation. Significantly, we identified two novel proteins (C20orf201 and TEX19) as putative meiosis-associated proteins that may have enhanced presence in cancer and the potential to be immunogenic. In summary, this research into germline restricted genes in cancer vs normal tissues has identified two previously uncharacterised proteins that are likely to be relevant for the biology, behaviour or therapy of some cancers and has also identified a cohort of further genes that warrant further scientific exploration.

Details

Iaith wreiddiolSaesneg
Sefydliad dyfarnu
Goruchwylydd / Goruchwylwyr / Cynghorydd
Noddwyr traethodau hir
  • North West Cancer Research
Dyddiad dyfarnuIon 2015