Position- and base pair-specific comparison of p53 mutation spectra in human tumors: elucidation of relationships between organs for cancer etiology.

摘要: A new approach to analyze the p53 mutation database of European Molecular Biology Laboratory for a comparison spectra is described, with aim investigating organ specificity etiological factors and putative organ-to-organ relationships in cancer pathogenesis. The number entries each nucleotide- base-pair substitution-specific was divided by total tumors analyzed. For pair, difference mutation-specific frequency differences calculated. Resulting values could range from 0 (full concordance) 2 discordance). Skin, lung, urinary bladder showed highly independent (maximum discordance value = 1.48 skin versus brain), agreement presence specific responsible large respective (UV light, smoking, aromatic amines). three organs smallest sum were mammary gland (breast), colon esophagus. minimum 0.95, stomach colon. these organs, common, possibly also endogenous, risk be postulated as contributing observed spectrum. remaining cancers (ovary, sarcoma, leukemia/lymphoma, brain, head neck, stomach, order or increasing discordance) intermediate mix values. Reasons close relationship some other marked others are discussed. Exclusion "hot-spot" mutations did not markedly alter relationships, indicating that selective growth advantage does cover up basis It expected much more insight into carcinogenesis gained further exploratory analyses databases.