COMPUTER-PROGRAM FOR THE ANALYSIS OF MUTATIONAL SPECTRA - APPLICATIONTO P53 MUTATIONS

Mutations in the p53 oncogene are extremely common in human cancers, a nd environmental exposure to mutagenic agents may play a role in the f requency and nature of the mutations. Differences in the patterns of p 53 mutations have been observed for different tumor types. It is not t rivial to determine if the differences observed in two mutational spec tra are statistically significant. To this end, we present a computer program for comparison of two mutational spectra. The program runs on IBM-compatible personal computers and is freely available. The input f or the program is a text file containing the number and nature of muta tions observed in the two spectra. The output of the program is a P va lue, which indicates the probability that the two spectra are drawn fr om the same population. To demonstrate the program, the mutational spe ctra of single base substitutions in the p53 gene are compared in (i) bladder cancers from smokers and non-smokers, (ii) small-cell lung can cers, non-small-cell lung cancers and colon cancers and (iii) hepatoce llular carcinomas from high- and low-aflatoxin exposure groups. p53 mu tations differ in several important aspects from a typical mutational spectra experiment, where a homogeneous population of cells is treated with a specific mutagen and mutations at a specific locus are recover ed by phenotypic selection. The means by which p53 mutations are recog nized is by the appearance of a cancer, and this phenotype is very com plex and varied.