期刊
CANCER RESEARCH
卷 74, 期 6, 页码 1814-1821出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-13-1446
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资金
- American Cancer Society [117842-PF-09-261-01-TBG]
- Abby S. and Howard P. Milstein Innovation Award for Melanoma and Skin Cancer Research
- Cancer Prevention Research Institute of Texas Scholar in Cancer Research
Although many DNA aberrations in melanoma have been well characterized, including focal amplification and deletions of oncogenes and tumor suppressors, broad regions of chromosomal gain and loss are less well understood. One possibility is that these broad events are a consequence of collateral damage from targeting single loci. Another possibility is that the loss of large regions permits the simultaneous repression of multiple tumor suppressors by broadly decreasing the resident gene dosage and expression. Here, we test this hypothesis in a targeted fashion using RNA interference to suppress multiple candidate residents in broad regions of loss. We find that loss of chromosome regions 6q, 10, and 11q21-ter is correlated with broadly decreased expression of most resident genes and that multiple resident genes impacted by broad regional loss of chromosome 10 are tumor suppressors capable of affecting tumor growth and/or invasion. We also provide additional functional support for Ablim1 as a novel tumor suppressor. Our results support the hypothesis that multiple cancer genes are targeted by regional chromosome copy number aberrations. (C) 2014 AACR.
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