Coordinated Tumor Suppression by Chromosome 8p

Abstract

In this issue of Cancer Cell, Cai et al. use genome editing to study 8p deletions in a mammary epithelial cell model and show that 8p loss of heterozygosity (LOH) attenuates the action of several genes that collectively promote cell invasion and enhance cellular sensitivity to autophagy inhibitors.

Figure 1. Different Configurations of Genomic Deletions Found in Human Cancer

(A) Depicted is the classic “two-hit” mechanism of complete inactivation of a tumor-suppressor gene (TSG) by focal deletions in both alleles. This is commonly seen for the CDKN2A/B locus on chromosome 9q, with short interstitial deletions encompassing only a few genes. (B) Mutation of one TSG allele, deletion of second allele together with >100 neighboring genes. In tumors, this combination is the most frequent mode for alterations of 17p in which mutant TP53 on one allele acts in the context of a large deletion affecting the second TP53 allele and decreasing expression of hundreds of surrounding genes. (C) Hemizygous deletion of hundreds of genes simultaneously, as found for 8p. Because no recurrent somatic nucleotide variants (SNVs) have been identified in the remaining 8p arm, the loss of this region likely acts through cumulative haploinsufficiency of affected genes.