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Molecular Cancer Research
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Mutational Landscape of the Essential Autophagy Gene BECN1 in Human Cancers

Saurabh V. Laddha, Shridar Ganesan, Chang S. Chan and Eileen White
Saurabh V. Laddha
1Rutgers Cancer Institute of New Jersey; 2Department of Medicine, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick; and 3Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey
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Shridar Ganesan
1Rutgers Cancer Institute of New Jersey; 2Department of Medicine, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick; and 3Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey
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Chang S. Chan
1Rutgers Cancer Institute of New Jersey; 2Department of Medicine, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick; and 3Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey
1Rutgers Cancer Institute of New Jersey; 2Department of Medicine, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick; and 3Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey
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Eileen White
1Rutgers Cancer Institute of New Jersey; 2Department of Medicine, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick; and 3Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey
1Rutgers Cancer Institute of New Jersey; 2Department of Medicine, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick; and 3Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey
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DOI: 10.1158/1541-7786.MCR-13-0614 Published April 2014
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Abstract

Evidence suggests that the catabolic process of macroautophagy (autophagy hereafter) can either suppress or promote cancer. The essential autophagy gene ATG6/BECN1 encoding the Beclin1 protein has been implicated as a haploinsufficient tumor suppressor in breast, ovarian, and prostate cancers. The proximity of BECN1 to the known breast and ovarian tumor suppressor breast cancer 1, early onset, BRCA1, on chromosome 17q21, has made this determination equivocal. Here, the mutational status of BECN1 was assessed in human tumor sequencing data from The Cancer Genome Atlas (TCGA) and other databases. Large deletions encompassing both BRCA1 and BECN1, and deletions of only BRCA1 but not BECN1, were found in breast and ovarian cancers, consistent with BRCA1 loss being a primary driver mutation in these cancers. Furthermore, there was no evidence for BECN1 mutation or loss in any other cancer, casting doubt on whether BECN1 is a tumor suppressor in most human cancers.

Implications: Contrary to previous reports, BECN1 is not significantly mutated in human cancer and not a tumor-suppressor gene, as originally thought.

Visual Overview: http://mcr.aacrjournals.org/content/early/2014/04/01/1541-7786.MCR-13-0614/F1.large.jpg. Mol Cancer Res; 12(4); 485–90. ©2014 AACR.

This article is featured in Highlights of This Issue, p. 477

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Research Online (http://mcr.aacrjournals.org/).

  • Received November 19, 2013.
  • Revision received January 7, 2014.
  • Accepted January 13, 2014.
  • ©2014 American Association for Cancer Research.
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Molecular Cancer Research: 12 (4)
April 2014
Volume 12, Issue 4
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Mutational Landscape of the Essential Autophagy Gene BECN1 in Human Cancers
Saurabh V. Laddha, Shridar Ganesan, Chang S. Chan and Eileen White
Mol Cancer Res April 1 2014 (12) (4) 485-490; DOI: 10.1158/1541-7786.MCR-13-0614

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Mutational Landscape of the Essential Autophagy Gene BECN1 in Human Cancers
Saurabh V. Laddha, Shridar Ganesan, Chang S. Chan and Eileen White
Mol Cancer Res April 1 2014 (12) (4) 485-490; DOI: 10.1158/1541-7786.MCR-13-0614
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