Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma.

Abstract

We identified germline p53 mutations in seven of 235 (3.0%) children with osteosarcoma. Four of these mutations were found in patients who did not have first-degree relatives with cancer. Although genetic transmission of the altered p53 gene could not be tested in this survey because of how it was designed, it is possible that predictive testing for p53 mutations could identify unaffected relatives of gene carriers who also have a high risk for the development of cancer. This study provides evidence for the importance of considering children with osteosarcoma for predictive testing for germline p53 mutations.

Relative frequency and morphology of cancers in carriers of germline TP53 mutations

“…Thus, published reports include studies of the incidence of germline TP53 mutations among series of patients with tumours typical of LFS thereby increasing the frequency of these cancers overall. Such studies include brain tumours (Kyritis et al, 1994;Chen et al, 1995;Zhou et al, 1999) breast cancer (Bùrresen et al, 1992;Sidransky et al, 1992;Prosser et al, 1992) sarcomas (Toguchida et al, 1992;McIntyre et al, 1994;Diller et al, 1995;Ayan et al, 1997) and adrenocortical carcinoma (Wagner et al, 1994;Sameshima et al, 1992;Varley et al, 1999). Some patients and families were selected for analysis of germline TP53 status on the basis of clusters of cancers typical of LFS e.g.…”

A detailed study of loss of heterozygosity on chromosome 17 in tumours from Li – Fraumeni patients carrying a mutation to the TP53 gene

“…Over half of all families conforming to the de®nition of classic LFS and approximately one quarter of those which are Li ± Fraumeni-like (LFL, Birch et al, 1994) carry germline mutations to the TP53 gene (Malkin et al, 1990;Birch et al, 1994;Frebourg et al, 1995;Varley et al, 1997). Furthermore, a signi®cant proportion of patients with tumours which are typical of those seen in Li ± Fraumeni syndrome have also been shown to carry TP53 germline mutations at an increased frequency Sameshima et al, 1992;Toguchida et al, 1992;Brugieres et al, 1993;Kyritsis et al, 1994;McIntyre et al, 1994;Wagner et al, 1994;Chen et al, 1995;Diller et al, 1995;Li et al, 1995). TP53 is considered to be a tumour suppressor gene (Hollstein et al, 1991;Levine et al, 1991;Lane, 1992), and as such some tumours from patients with germline TP53 mutations have been analysed for loss of heterozygosity (LOH).…”

Tissue-specific expression of SV40 in tumors associated with the Li–Fraumeni syndrome

“…Osteosarcoma is another commonly observed component tumor of LFS. Furthermore, approximately 10% of patients with sporadic osteosarcoma harbor germline mutations of either the RB1 or p53 tumor suppressor genes (Miller et al, 1996;McIntyre et al, 1994). Renal cell carcinoma is more commonly associated with von Hippel ± Lindau disease than LFS; nevertheless, it too has been reported to occur in LFS families (Sedlacek et al, 1998).…”