Source: Hospital of Stomatology
Written by: Hospital of Stomatology
Edited by: Wang Dongmei
Recently, Associate Professor Baoshan Xu from Hospital of Stomatology of Sun Yat-sen University (recruited by the “One Hundred Talents Program” of Sun Yat-sen University) published a research article to find cancer cells may streamline their genomes in order to proliferate more easily, in PLoS Genetics (IF:6.100), which was collaborated with Prof. Jennifer L. Gerton from the Stowers Institute for Medical Research. (Link to the article:
http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006771). This discovery was widely reported by many notable science media, such as The Scientist, ScienceDaily, and Ebiotrade, etc.
Human chromosomes are stained blue (DAPI) with ribosomal DNA in green (FISH probe);
Image courtesy of Tamara Potapova, Ph.D.
The ribosomal DNA (rDNA) encodes the ribosomal RNAs (rRNA) needed to make ribosomes for protein synthesis and cellular proliferation. Ribosomal DNA is one of the most variable regions in the human genome individually with respect to copy number. Despite the importance of rDNA for cellular function, we know virtually nothing about what governs its copy number and stability in the mammalian genome due to challenges associated with mapping and analysis. In the study, we applied computational biology and droplet digital PCR approaches to measure rDNA copy number in normal and cancer states in human and mouse genomes. We find that copy number and sequence can change in cancer genomes. Counterintuitively, human cancer genomes show a loss of copies, accompanied by copy number co-variation of many other genes. The sequence can also be more variable in the cancer genome. Cancer genomes with lower copies have mutational evidence of mTOR hyperactivity. The Pten phosphatase is a tumor suppressor that is critical for genome stability and a negative regulator of the mTOR kinase pathway. Surprisingly, but consistent with the human cancer genomes, hematopoietic cancer stem cells from a Pten-/- mouse model for leukemia have lower rDNA copy number than normal tissue, despite increased proliferation, rRNA production, and protein synthesis. Loss of copies occurs at the early stage of tumorigenesis and is associated with hypersensitivity to DNA damage. Therefore, copy loss is a recurrent feature in cancers associated with mTOR activation. Ribosomal DNA copy number may be a simple and useful indicator of whether a cancer will be sensitive to DNA damaging chemotherapeutics.
