Imprinted survival genes preclude loss of heterozygosity of chromosome 7 in cancer cells

Oncocytic variants of follicular thyroid carcinomas show a near-homozygous genome. Remarkably, homozygosity of chromosome 7 has never been observed which suggests that retention of heterozygosity is essential for cells. We hypothesized that cell survival genes are genetically imprinted on either of two copies of chromosome 7 which thwarts loss of heterozygosity at this chromosome in cancer cells. We identified 6 genes on chromosome 7 which demonstrated allele-specific expression. Subsequent knockdown of gene expression showed that CALCR, COPG2, GRB10, KLF14, MEST and PEG10 were essential for cancer cell survival resulting in reduced cell proliferation, G1-phase arrest and increased apoptosis. We propose that imprinted cell survival genes provide a genetic basis for retention of chromosome 7 heterozygosity in cancer cells. 7 thyroid carcinoma samples with stable genomic profiles, 7 thyroid carcinomas with near homozygous genomes and 2 adrenal cortical carcinoma samples with near homozygous genomes. Sample selection was based on previous results; sample ID's used here are identical to those used in the previous study (Corver et al., Genes Chromosomes.Cancer, 2014).