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Report analyzes global market for pancreatic cancer drugs

January 19, 2016

The researchers had previously noted that the older L1s have a lower CpG content than the younger sequences as expected, but here they observed two particularly striking features: "The overall mutation rate in the older fossil sequences dropped dramatically," said Furano, indicating a certain CpG content threshold is required to affect the non-CpG mutation rate. "And most provocatively, the types of mutations changed significantly."

This means that CpGs are not only promoting mutations, but they are also influencing how the non-CpG sequences around them are being mutated, an extension of what the authors call the "CpG effect." These findings strongly support the hypothesis that the co-variation of CpG content and non-CpG mutation rate is a property of the DNA sequence itself, and not a result of the chromosomal location.

"Intriguingly, the CpG effect revealed by our studies mimics the altered mutational state that has been demonstrated for certain cancers," Furano noted. Furthermore, the authors expect that this work will open the door to future studies investigating the mechanisms by which CpGs exert their influence on mutation rate and how this is involved in the critical process of genome maintenance. Scientists from National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) contributed to this study.

Source: Cold Spring Harbor Laboratory