Cancer cells restructure genomes to reproduce more easily

Contributed by Nguyet Kong

A group at Stowers Institute in Kansas City recently published their study in PLos Genetics describing that cancer cells restructuring in the ribosomal DNA to more easily reproduce copies. The rDNA cellular functions include regulating gene expression, chromosome organization, and chromatin factors. There not much known about the stability of rDNA, but the researchers believe more data can be obtained by using digital droplet PCR to measure rDNA copies. Extracted genomic DNA from 3 mouse strains tissues samples and from different organ types. The researchers first measured the copies between the mouse strain and averaging the numbers. C57BL/6 mouse strain was 156 and DBA/2J was 123. The mean copy number for CD-1 was145 with higher individual variation. The researchers then found changed in the mtDNA copy in different tissues not equivalents to the changed reported in the rDNA copies. The researchers wanted to confirm their finding in cancer cells in human, so they obtained whole genome sequencing from 162 across eight tumor types and also analyzed rDNA copies from the sequencing data. The researchers have found a significant reduction in copies for tumor genomes in 3 of the 8 groups, suggesting low copy number at the rDNA was selected in some cancer types.

Next, the researchers wanted to see if mTOR function will suppress tumor function in PTEN could influence rDNA copies. They use a mouse model Pten leukemia to assess rDNA copies in hematopoietic stem cells (HSCs), which they did sequence and droplet PCR. This verified that the loss of PTEN is indicative of mTOR activation, and they confirm HSC cells and ribosome genesis can occur with 30 to 40 fewer rDNA repeats. The researchers suggest that instability of the genome can make the cells susceptible to chemo with DNA damaging drugs.

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