DELETIONS AND INSERTIONS IN THE P53 TUMOR-SUPPRESSOR GENE IN HUMAN CANCERS - CONFIRMATION OF THE DNA-POLYMERASE SLIPPAGE MISALIGNMENT MODEL

We analyzed all published deletions and insertions in the p53 gene to assess the relevance of mutagenesis models, Almost all deletions and i nsertions can be explained by one or more of the following DNA sequenc e features: monotonic base runs, adjacent or nonadjacent repeats of sh ort tandem sequences, palindromes, and runs of purines or pyrimidines (homocopolymer runs), Increased length of monotonic runs correlates po sitively with increased frequency of events, Complex frameshift mutati ons can be explained by the formation of quasi-palindromes, with misma tch excision and replication using one strand of the palindrome as a t emplate, Deletions and insertions in the p53 tumor suppressor gene may reflect both spontaneous and carcinogen-induced mutagenesis.