The search for cis-regulatory driver mutations in cancer genomes

Rebecca C Poulos _, Mathew A Sloane, Luke B Hesson and Jason W. H. Wong

PDF  |  HTML  |  How to cite

Oncotarget. 2015; 6:32509-32525. https://doi.org/10.18632/oncotarget.5085

Metrics: PDF 3169 views  |   HTML 3873 views  |   ?  


Rebecca C. Poulos1, Mathew A. Sloane1, Luke B. Hesson1, Jason W. H. Wong1

1Prince of Wales Clinical School and Lowy Cancer Research Centre, UNSW Australia, Sydney, Australia

Correspondence to:

Rebecca C. Poulos, e-mail: [email protected]

Jason W. H. Wong, e-mail: [email protected]

Keywords: promoter, enhancer, cancer, somatic mutation, cis-regulation

Received: June 11, 2015     Accepted: August 06, 2015     Published: August 20, 2015


With the advent of high-throughput and relatively inexpensive whole-genome sequencing technology, the focus of cancer research has begun to shift toward analyses of somatic mutations in non-coding cis-regulatory elements of the cancer genome. Cis-regulatory elements play an important role in gene regulation, with mutations in these elements potentially resulting in changes to the expression of linked genes. The recent discoveries of recurrent TERT promoter mutations in melanoma, and recurrent mutations that create a super-enhancer regulating TAL1 expression in T-cell acute lymphoblastic leukaemia (T-ALL), have sparked significant interest in the search for other somatic cis-regulatory mutations driving cancer development. In this review, we look more closely at the TERT promoter and TAL1 enhancer alterations and use these examples to ask whether other cis-regulatory mutations may play a role in cancer susceptibility. In doing so, we make observations from the data emerging from recent research in this field, and describe the experimental and analytical approaches which could be adopted in the hope of better uncovering the true functional significance of somatic cis-regulatory mutations in cancer.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 5085