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Published on: July 22, 2020
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Non-coding driver mutations in human cancer
Kerryn Elliott1, Erik Larsson2
1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Nature Reviews. Cancer
|July 7, 2021
Summary
Cancer develops from random mutations, with driver mutations being key. While protein-coding mutations are well-studied, non-coding driver mutations are rare but significant, posing detection challenges.
Area of Science:
- Genomics
- Cancer Biology
- Evolutionary Medicine
Background:
- Tumorigenesis arises from random mutations and evolutionary selection of driver mutations.
- Exome sequencing has identified numerous protein-coding somatic driver mutations, some clinically actionable.
- Whole-genome analysis is advancing, enabling exploration of non-coding regions for driver mutations.
Purpose of the Study:
- To review recent findings on non-coding driver mutations.
- To discuss the challenges in identifying selection signals in non-coding DNA.
- To explore reasons for the apparent infrequency of non-coding driver events.
Main Methods:
- Review of current literature on cancer genomics and driver mutation discovery.
- Analysis of challenges in detecting positive selection in non-coding DNA.
- Comparative analysis of coding versus non-coding mutation landscapes.
Main Results:
- Non-coding driver mutations appear relatively infrequent compared to coding mutations.
- Despite their rarity, several notable non-coding driver mutations have been identified.
- Detecting selection signals in the vast non-coding DNA remains a significant challenge.
Conclusions:
- The landscape of cancer driver mutations is expanding beyond protein-coding regions.
- Further research is needed to overcome challenges in identifying non-coding driver mutations.
- Understanding non-coding drivers is crucial for a comprehensive view of tumorigenesis.
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