Mutational landscape of the essential autophagy gene BECN1 in human cancers.
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.


CONCLUSIONS
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.
Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903-2681. epwhite@cinj.rutgers.edu.
Saurabh V
SV
Laddha
Shridar
S
Ganesan
Chang S
CS
Chan
Eileen
E
White
D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D001343:Autophagy / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D000071186:Beclin-1; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D018095:Germ-Line Mutation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D019313:BRCA1 Protein; D000071186:Beclin-1; D008565:Membrane Proteins