Screening for germ line p53 mutations in children with malignant tumors and a family history of cancer.

We have undertaken a routine investigation of the p53 status for all the children treated at our institution either affected by multiple tumors or whose family displays at least one second degree relative or less, affected by cancer before the age of 45 years. We report here on the first set of ten such families, eight of which were identified through a proband with sarcoma. p53 exons 5 to 8 have been sequenced following polymerase chain reaction amplification performed on DNA isolated from total blood. A missense mutation affecting codons 248, 273, and 282 was identified in three families. The mutation was inherited in these three families and was detected in unaffected members. In seven families no mutation was detected in exons 5 to 8.

[1]  C. Cordon-Cardo,et al.  p53 mutations in human bladder cancer: Genotypic versus phenotypic patterns , 1994, International journal of cancer.

[2]  S. Friend,et al.  Cancer risks from germline p53 mutations. , 1992, The Journal of clinical investigation.

[3]  L. Strong,et al.  Segregation analysis of cancer in families of childhood soft-tissue-sarcoma patients. , 1992, American journal of human genetics.

[4]  S. Friend,et al.  Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R. Weichselbaum,et al.  Prevalence and spectrum of germline mutations of the p53 gene among patients with sarcoma. , 1992, The New England journal of medicine.

[6]  S. Friend,et al.  Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. , 1992, The New England journal of medicine.

[7]  J. Yokota,et al.  Detection of novel germ-line p53 mutations in diverse-cancer-prone families identified by selecting patients with childhood adrenocortical carcinoma. , 1992, Journal of the National Cancer Institute.

[8]  Thierry Soussi,et al.  TP53 tumor suppressor gene: A model for investigating human mutagenesis , 1992, Genes, chromosomes & cancer.

[9]  L. Strong,et al.  A germ line mutation in exon 5 of the p53 gene in an extended cancer family. , 1991, Cancer research.

[10]  J. Fraumeni,et al.  Follow-up study of twenty-four families with Li-Fraumeni syndrome. , 1991, Cancer research.

[11]  V. Sheffield,et al.  Identification of a germ-line mutation in the p53 gene in a patient with an intracranial ependymoma. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Margaret Robertson,et al.  Identification and characterization of the familial adenomatous polyposis coli gene , 1991, Cell.

[13]  G. Lenoir,et al.  Familial breast-ovarian cancer locus on chromosome 17q12-q23 , 1991, The Lancet.

[14]  A. Levine,et al.  The p53 tumour suppressor gene , 1991, Nature.

[15]  R. Fisher,et al.  A prospective genetic study of complete and partial hydatidiform moles. , 1991, American journal of obstetrics and gynecology.

[16]  M. King,et al.  Linkage of early-onset familial breast cancer to chromosome 17q21. , 1990, Science.

[17]  W. Blattner,et al.  Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li–Fraumeni syndrome , 1990, Nature.

[18]  L. Strong,et al.  Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. , 1990, Science.

[19]  W. Blattner,et al.  A cancer family syndrome in twenty-four kindreds. , 1988, Cancer research.

[20]  Stephen H. Friend,et al.  A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma , 1986, Nature.

[21]  H. B. Marsden,et al.  Excess risk of breast cancer in the mothers of children with soft tissue sarcomas. , 1984, British Journal of Cancer.