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Genes (Basel). 2017 May 25;8(6). pii: E151. doi: 10.3390/genes8060151.

MYC Deregulation in Primary Human Cancers.

Author information

1
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada. manpreet.kalkat@mail.utoronto.ca.
2
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada. manpreet.kalkat@mail.utoronto.ca.
3
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada. jason.demelo@uhnresearch.ca.
4
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada. ashley.hickman@mail.utoronto.ca.
5
Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada. ashley.hickman@mail.utoronto.ca.
6
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada. corey.lourenco@mail.utoronto.ca.
7
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada. corey.lourenco@mail.utoronto.ca.
8
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada. cornelia.redel@mail.utoronto.ca.
9
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada. cornelia.redel@mail.utoronto.ca.
10
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada. diana.resetca@mail.utoronto.ca.
11
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada. diana.resetca@mail.utoronto.ca.
12
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada. aaliya.tamachi@utoronto.ca.
13
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada. william.tu@mail.utoronto.ca.
14
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada. william.tu@mail.utoronto.ca.
15
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada. lpenn@uhnresearch.ca.
16
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada. lpenn@uhnresearch.ca.

Abstract

MYC regulates a complex biological program by transcriptionally activating and repressing its numerous target genes. As such, MYC is a master regulator of many processes, including cell cycle entry, ribosome biogenesis, and metabolism. In cancer, the activity of the MYC transcriptional network is frequently deregulated, contributing to the initiation and maintenance of disease. Deregulation often leads to constitutive overexpression of MYC, which can be achieved through gross genetic abnormalities, including copy number alterations, chromosomal translocations, increased enhancer activity, or through aberrant signal transduction leading to increased MYC transcription or increased MYC mRNA and protein stability. Herein, we summarize the frequency and modes of MYC deregulation and describe both well-established and more recent findings in a variety of cancer types. Notably, these studies have highlighted that with an increased appreciation for the basic mechanisms deregulating MYC in cancer, new therapeutic vulnerabilities can be discovered and potentially exploited for the inhibition of this potent oncogene in cancer.

KEYWORDS:

MYC; cancer; cell signaling; deregulation; enhancers; gene amplification; translocation

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