Guangzhou Health Center found that the Cancer-Testis gene can cause persistent chromosomal instability

The expression of the cancer-testis (CT) protein is actually an epigenetic phenomenon
that is easily overlooked.
Meiosis-related genes that are activated in cancer may also be associated with
chromosomal instability at the time of tumorigenesis.
Among the cohesin complex proteins necessary for chromosome separation during mitosis and meiosis, the cohesin (mei-cohesin) protein subunit SMC1B of germ cells, STAG3, REC8, and RAD21L are also expressed in some cancers, and to elucidate the potential role of these proteins in cancer genomic instability, two approaches were used in this study: 1 epigenomic studies in normal primate testicular tissue; 2.
Comparative analysis of differences between human cancer cells and immortalized cells after ectopic expression of meiotic cohensin protein
complexes.

ChIP-on-ChEP-seq experiments were performed on the testicular tissues of crab-molgus macaques, and it was found that there was an overlapping pattern
of the binding of the mei-cohesin subunit to the germline chromosomes.
They are largely the same site as BORIS/CTCFL binding rather than the somatic cohesin-associated CTCF site
.
Reconstructing the two MEI-Cohesin complexes in human cell lines showed that they were able to stably bind chromosome whole genomes and affect somatic gene expression
.
While ectopic induced expression of the REC8 complex has limited effect on mitosis in cells, expression of the RAD21L complex results in a large number of chromosomal recombinations, reminiscent of axial element assembly in pre-meiosis), leading to DNA damage, Mitotic delay, false separation, and polyploidy
.
In addition, most cells expressing RAD21Lcohesin remain highly viability during prolonged blockade and resume proliferation with a large number of chromosomal mutations
after removal of inducers.

This study provides a plausible explanation
for the insufficient expression of RAD21L1 in tumors.
It has also been shown that CT gene may be a major inducer of
chromosomal instability and non-polyploid phenomena in somatic and precancerous cells.

Boukaba Abdelhalim, associate researcher at Guangzhou Health Center, is the first author and Alexander Strunnikov is the corresponding author
.
The research was supported
by the National Key R&D Program and Guangdong Province Leading Talents.