To characterize the role of p53 in the development of testis cancer, we looked for mutations in the coding sequences of the p53 gene. DNA was obtained both from familial and sporadic testis cancer specimens, as well as from peripheral blood from members of a testis cancer kindred. Mutations in the p53 gene were screened using a combination of constant denaturant gel electrophoresis and single-strand conformational polymorphism analysis, 2 screening methods that can detect single base changes. Abnormalities detected by these methods were confirmed by sequencing of the corresponding cloned polymerase chain reaction products. All conserved regions of the p53 coding sequences were examined, encompassing all previously reported sites of mutations. No mutations were found in any of 22 germ cell cancers of the testis or in the germline DNA of 17 members of the testis cancer family. This is in striking contrast to most other human cancers, in which mutations of p53 are the most commonly described molecular event associated with tumorigenesis. We conclude that dysfunction of tumor suppressor gene or genes other than p53 may prove to play an important role in the development of germ cell cancers of the testis.

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This work was supported by Physicians Services, Inc. D. H. is supported in part by the Medical Research Council of Canada. D. M. is a scholar of the Medical Research Council of Canada, a Young Investigator (Abbor Pharmaceuticals), and is supported in part by the Medical Research Council of Canada and the National Cancer Institute of Canada.

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