Good news! Cancer is history (soon)! "Cancer mystery dating to 19th century finally has an answer"
"The vast majority of cancer cells have too few or too many copies of some chromosomes, a state known as aneuploidy. But for decades, researchers have debated whether aneuploidy promotes the growth of cancers, or is simply a side effect of cancer cells’ fast growth. ...
Now, researchers ... have found — thanks to a computational tool they developed — that aneuploidy does drive cancer progression. Using that method, the scientists compared large chromosome changes in tumor cells from more than 10,000 cancer patients and identified key chromosome regions that, when duplicated or deleted, were harmful or beneficial to tumor cells. The work also revealed a new role for a known cancer gene called WRN — a result that, the team said, shows how this type of analysis can reveal new insight into cancer biology. ...
More recently, studies have shown that aneuploidies — which also include duplications or deletions of entire arms of chromosomes — are present in almost 90 percent of human cancers, often appear early in cancer, and are associated with worse clinical outcomes. ...
In nearly one-third of all cancers in TCGA [The Cancer Genome Atlas], one arm of chromosome 8 is missing, but researchers had never been sure why this aneuploidy is so common. The study showed that deletions on chromosome 8 were more likely to include the cancer gene WRN than other areas of DNA, suggesting that it has a particularly large impact. ..."
More recently, studies have shown that aneuploidies — which also include duplications or deletions of entire arms of chromosomes — are present in almost 90 percent of human cancers, often appear early in cancer, and are associated with worse clinical outcomes. ...
In nearly one-third of all cancers in TCGA [The Cancer Genome Atlas], one arm of chromosome 8 is missing, but researchers had never been sure why this aneuploidy is so common. The study showed that deletions on chromosome 8 were more likely to include the cancer gene WRN than other areas of DNA, suggesting that it has a particularly large impact. ..."
From the abstract:
"Aneuploidies—whole-chromosome or whole-arm imbalances—are the most prevalent alteration in cancer genomes. However, it is still debated whether their prevalence is due to selection or ease of generation as passenger events. Here we developed a method, BISCUT, that identifies loci subject to fitness advantages or disadvantages by interrogating length distributions of telomere- or centromere-bounded copy-number events. These loci were significantly enriched for known cancer driver genes, including genes not detected through analysis of focal copy-number events, and were often lineage specific. BISCUT identified the helicase-encoding gene WRN as a haploinsufficient tumour-suppressor gene on chromosome 8p, which is supported by several lines of evidence. We also formally quantified the role of selection and mechanical biases in driving aneuploidy, finding that rates of arm-level copy-number alterations are most highly correlated with their effects on cellular fitness. These results provide insight into the driving forces behind aneuploidy and its contribution to tumorigenesis."
Cancer aneuploidies are shaped primarily by effects on tumour fitness (no public access)
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