Using a polymerase chain reaction-single strand conformation polymorphism approach we analyzed 96 human primary breast tumors for the presence of mutations in exons 2, 5, 6, 7, 8, and 9 of the p53 gene. These exons have been shown to comprise highly conserved sequences and the portion including exons 5 through 9 is believed to be the target for over 90% of the acquired mutations in human cancer. Eighteen tumors of the 96 (18.7%) tested showed reproducibly a variant band indicative of a mutation. Most (15 tumors) of the mutations were single nucleotide substitutions and G:C to A:T transitions were prevalent (6 tumors), G:C to T:A transversions came next (4 tumors), and guanines were always on the nontranscribed strand. Concomitant loss of the wild type allele and mutation of the other copy was observed in only 3 of 18 mutated cases; this is consistent with the heterogeneous cellular composition of breast tumors. Furthermore p53 mutations were correlated to estrogen and/or progesterone receptor negative tumors, thus indicating their relationships to aggressive breast cancer. No association could be observed with DNA amplification events in these tumors.

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R. M. was supported by a predoctoral fellowship from the Association de la Recherche sur le Cancer; M. B. C. was supported by a predoctoral fellowship from the Comité Départemental de l'Hérault de la Ligue Nationale Contre le Cancer; L. S. was on exchange supported by a program from the EEC (Eureka). This work was in part funded by the Caisse Régionale d'Assurance Maladie, the Fédération Nationale des Centres de Lutte Contre le Cancer, and the Ligue Nationale de Lutte Contre le Cancer.

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