Germline TP53 mutations predispose to a rare familial cancer syndrome, the Li-Fraumeni Syndrome (LFS), characterized by the early onset of multiple cancers including childhood adrenocortical carcinomas, sarcomas and brain tumors, and breast and colon cancer in young adults.
Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer.
Germline mutations of the p53 coding region are present in approximately 50-70% of patients with Li-Fraumeni Syndrome (LFS), a rare hereditary disorder of familial and intraindividual clustering of different malignancies such as sarcoma (index tumor), breast cancer, brain tumors, leukemias, and adrenocortical carcinomas, the latter usually in young children.
In contrast to reported findings for other types of cancer, we found that mutations of the p53 gene in sarcomas are quite heterogeneous both in their distribution throughout the gene and in the type of genetic alterations that result.
In particular, the discovery of tumor suppressor gene syndromes, such as Rb1 gene and p53 gene defects manifested in "cancer families," were made possible by their association with sarcomas, otherwise rare tumors.
In the absence of Kras mutations, injury of the muscle with global deletion of p53 results in sarcomas with amplification of chromosomal regions encompassing the Met or Yap1 gene.
In this study we examined 63 methylcholanthrene (MCA)-induced sarcomas from C57BL/6N x C3H/HeN F1 (BCF1) or C3H/HeN x C57BL/6N F1 (CBF1) mice for p53 gene mutations and loss of heterozygosity (LOH) of chromosome 11.
In this study, p53 expression in the sarcoma tissues was analysed immunohistochemically using antibody PAb421 (Oncogene Science) and its relationship to DNA alterations was examined.
In this study, we assess the apparent generation effect on cancer incidence in ten extended families with P53 germline mutation, identified through probands diagnosed with childhood sarcoma.
Known genetic events in these tumors are mutations in TP53 (atypical fibroxanthoma and pleomorphic dermal sarcoma) and RAS (pleomorphic dermal sarcoma) genes, often having a UV signature.
Many malignancies display amplification of MDM genes encoding negative regulators of p53 and therefore much effort to date has concentrated on the development of molecules that inhibit MDM2, the most advanced of which are being tested in clinical trials for sarcoma, glioblastoma, bladder cancer and lung adenocarcinoma.
New germline mutations of the p53 gene are rare among patients with "sporadic" sarcoma but may be common in patients with sarcoma whose background includes either multiple primary cancers or a family history of cancer.