Abstract

BackgroundGerm cell tumours are uniquely associated with the gametogenic tissues of males and females. A feature of these cancers is that they can express genes that are normally tightly restricted to meiotic cells. This aberrant gene expression has been used as an indicator that these cancer cells are attempting a programmed germ line event, meiotic entry. However, work in non‐germ cell cancers has also indicated that meiotic genes can become aberrantly activated in a wide range of cancer types and indeed provide functions that serve as oncogenic drivers. Here, we review the activation of meiotic factors in cancers and explore commonalities between meiotic gene activation in germ cell and non‐germ cell cancers.ObjectivesThe objectives of this review are to highlight key questions relating to meiotic gene activation in germ cell tumours and to offer possible interpretations as to the biological relevance in this unique cancer type.Materials and MethodsPubMed and the GEPIA database were searched for papers in English and for cancer gene expression data, respectively.ResultsWe provide a brief overview of meiotic progression, with a focus on the unique mechanisms of reductional chromosome segregation in meiosis I. We then offer detailed insight into the role of meiotic chromosome regulators in non‐germ cell cancers and extend this to provide an overview of how this might relate to germ cell tumours.ConclusionsWe propose that meiotic gene activation in germ cell tumours might not indicate an unscheduled attempt to enter a full meiotic programme. Rather, it might simply reflect either aberrant activation of a subset of meiotic genes, with little or no biological relevance, or aberrant activation of a subset of meiotic genes as positive tumour evolutionary/oncogenic drivers. These postulates provide the provocation for further studies in this emerging field.

Highlights

  • Human gametogenesis generates spermatozoa and oocytes that may fuse to form a zygote

  • Can analysis of expression of a subset of selected meiotic genes be used as markers to indicate a bona fide meiotic entry signalling network?. Are these genes being activated independently of a full meiotic entry programme? And if so, what regulates their activation?. Do these genes provide meiotic-like functions that contribute to oncogenic maintenance, progression and therapeutic resistance in germ cell (GC) tumours, as they do in other cancer types? Here, we provide insight from recent studies on the role of meiotic genes in a wide range of cancers

  • One view is the embryologic theory of cancer, in which cancer cells acquire embryo-like characteristics that would explain the malignant features of cancer cells (Erenpreisa et al, 2015)

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Summary

INTRODUCTION

Human gametogenesis generates spermatozoa and oocytes that may fuse to form a zygote. There are pronounced differences in regulation and timing of gametogenesis in females and males, but both require a meiotic chromosome segregation programme to drive haploidization; in the foetal ovaries, a defined number of oocytes enter prophase I of meiosis I, whereas in the foetal testes, meiotic entry is inhibited until puberty and spermatozoa are subsequently produced continually (Jørgensen & Rajpert-De Meyts, 2014). The homologous chromosomes undergo a dramatic juxtapositioning to initiate pairing and alignment During this period, a specific meiotic recombination programme is initiated by the generation of DNA doublestranded breaks (DSBs) in one chromatid of one of the homologues (Humphryes & Hochwagen, 2014; Hunter, 2015; Gray & Cohen, 2016) (Fig. 1B).

Metaphase I
RNA pol II
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