TP53 somatic mutations are associated with somatic mitogenome substitutions but not indels in colorectal cancer cells.

Abstract

p53 is a tumour suppressor protein that is involved in many cancer-related processes. Growing evidence suggests that p53 also plays an important role in mitochondrial (mtDNA) maintenance. Somatic mitogenome mutations are frequently observed in colorectal cancer (CC) cells. Thus, it was important to determine whether somatic mtDNA changes are associated with TP53 mutational status. In the present study, we analysed the TP53 gene in 67 CC patients, for whom mitogenome haplotypes were previously described. In total, 134 TP53 sequences (of cancer and matched normal specimens) were determined using the dideoxy method. Nine hereditary polymorphisms in the TP53 gene were detected in normal colon cells. None of them (neither alleles, nor genotypes) was associated with somatic mitogenome mutations in CC cells. Moreover, 42 somatic TP53 mutations were found in approximately 36% of CC tissues. These somatic changes were significantly more frequent in CC cells with somatic mtDNA mutations (p=0.0069). Furthermore, we show that only mitochondrial somatic substitutions (p=0.0017), but not indels (p>0.05), were associated with somatic TP53 mutations. The results of the present study suggest that changes in TP53 may modify p53 properties, which may result in the accumulation of somatic substitutions in CC mitogenomes.