Chromosome 10, frequently lost in human melanoma, encodes multiple tumor-suppressive functions.
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.
Authors' Affiliation: Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
Lawrence N
LN
Kwong
Lynda
L
Chin
D000818:Animals; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D056915:DNA Copy Number Variations; D055785:Gene Knockdown Techniques; D016147:Genes, Tumor Suppressor; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008546:Melanoma, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000235:genetics; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics; D059467:Transcriptome
C107440:ABLIM1 protein, human; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D034741:RNA, Small Interfering