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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Family pedigree of Li-Fraumeni syndrome was investigated from probands with childhood adrenocortical carcinoma in Japan. From 47 probands, 7 families had 3 or more cancer cases at ages less than 45 years within the first generation; one satisfied Li's original criteria, two were acceptable because of multiple primary cancer in the probands, and others showed an aggregation of cancers with onsets at early ages, though no sarcoma of mesenchymal origin was found. A significantly higher occurrence of cancer in the mothers of the probands, especially of the breast, was consistent with reports from the USA, and liver cancer, osteosarcoma and lung cancer among family members under the age of 45 also showed a higher frequency than in the general population. Similarities and differences between Japanese and Caucasian cases are discussed.
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PMID:Familial aggregation of cancer from proband cases with childhood adrenal cortical carcinoma. 191 26

The cancer experience among 754 first-degree relatives (mothers, fathers, and siblings) of a population-based series of 177 children with soft tissue sarcoma is reported. The current study represents an extension of our earlier work in which the authors found an excess of breast cancer in the mothers of 143 of these children. There were 40 cancers among all first-degree relatives, compared with 24.82 expected (relative risk [RR] 1.61, P = 0.006). There was no excess in fathers, but an excess of borderline significance was seen in mothers (RR 1.67, P = 0.0545), and a significant excess in siblings (RR 4.55, P = 0.0002), mainly due to carcinoma of the breast and pediatric tumors. Results of a step forward Cox multivariate analysis identified three variables in the index child which were independently associated with high cancer risk in relatives, as follows: age younger than 24 months at diagnosis; histologic type, embryonal rhabdomyosarcoma or other and unspecified soft tissue sarcoma; and male sex. It was possible, therefore, to identify a subgroup of children whose relatives are at high risk of early onset cancer (RR in this group 10.14). The pattern of cancers is consistent with the Li-Fraumeni syndrome. The authors conclude that a marked proportion of childhood soft tissue sarcoma has a genetic basis.
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PMID:Cancer in the families of children with soft tissue sarcoma. 222 80

Inappropriate expression of Met, the receptor for hepatocyte growth factor/scatter factor, has been implicated in sarcomagenesis via an autocrine mechanism. Sarcomas occur at high frequency in individuals with Li-Fraumeni syndrome as well as in p53-deficient mice. Here we show that these tumors express high levels of Met. Moreover, late passage fibroblast cell lines established from p53-deficient animals overexpress Met and can be tumorigenic in athymic nude mice, suggesting that progression occurs in vitro. The tumor explants display increased hepatocyte growth factor/scatter factor expression and Met turnover, indicating that autocrine Met activation contributes to tumor progression. Thus, the loss of wild-type p53 appears to greatly enhance the opportunity for inappropriate Met expression. Loss of p53 function does not by itself cause transformation, but inappropriate Met expression may be an important factor in sarcomagenesis.
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PMID:Met proto-oncogene product is overexpressed in tumors of p53-deficient mice and tumors of Li-Fraumeni patients. 772 66

The case is presented of a 26-year-old woman with myxoid liposarcoma of the right breast who developed a relapse with anaplastic spindle-cell mesenchymal tumor 7 months after primary therapy. Additionally, 13 months later a bilateral adeno-carcinoma of differing histological grade occurred in the breasts. To the best of our knowledge, no comparable sarcoma-carcinoma sequence in the mammary gland has been reported. For this reason this case is discussed, with special emphasis on possible causative factors and the relationship to the Li-Fraumeni syndrome.
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PMID:[Bilateral breast carcinoma after recurrent myxoid liposarcoma of the breast]. 779 76

We report a family with the Li-Fraumeni syndrome (LFS) in whom we have been unable to detect a mutation in the coding sequence of the p53 gene. Analysis of linkage to three polymorphic markers within p53 enabled direct involvement of p53 to be excluded. This is the first example of a LFS family in whom exclusion of p53 has been possible. Four affected members of the family with sarcoma or premenopausal breast cancer showed increased expression of p53 protein in their normal tissues as detected by immunohistochemistry. It therefore appears that the LFS phenotype has been conferred by an aberrant gene, showing a dominant pattern of inheritance, which may be acting to compromise normal p53 function rather than by a mutation in p53 itself. In order to try to determine the chromosomal location of this putative gene, we have carried out studies of linkage to candidate loci. By these means we have excluded involvement of Rb1 and BRCA1 on chromosomes 13q and 17q respectively. The MDM2 oncogene on chromosome 12q was considered to be the prime candidate as MDM2 is amplified in sarcomas and the MDM2 product binds to p53. Furthermore, p53 mutation and amplification of MDM2 have been shown to be mutually exclusive events in tumour development. Linkage analysis to two polymorphic markers within MDM2 yielded a three-point LOD score of -5.4 at a recombination fraction theta equal to zero. Therefore MDM2 could be excluded. It is possible that the gene which is responsible for cancer susceptibility in this family, possibly via interaction with p53, will be important in the histogenesis of breast cancer in general. We are now carrying out further studies to locate and identify this gene.
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PMID:Linkage studies in a Li-Fraumeni family with increased expression of p53 protein but no germline mutation in p53. 798 Oct 72

The entire coding sequence of the p53 gene was analysed for the presence of mutations in 12 families conforming to a restricted definition of Li-Fraumeni syndrome (classic LFS) and nine families with features of LFS conforming to a broader definition. Mutations were detected in seven families. Six were point mutations with one each affecting codons 175, 180, and 220 and three affecting codon 248. The seventh was a deletion/insertion mutation in exon 4. Germline mutations in p53 were a feature of families which included children with rhabdomyosarcoma and/or adrenal cortical carcinoma. Germline p53 mutations were detected in six of the nine families with such tumors. An analysis of these 7 mutations, together with 34 published examples, showed that more than one-half were transitions at CpG dinucleotides, suggesting that the majority of germline p53 mutations may arise as a result of spontaneous events. The most common cancers occurring in the 41 families with germline p53 mutations, in common with classic LFS, were bone and soft tissue sarcoma, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma, although less than one-half of the probands with germline p53 mutations came from classic LFS families. More than one-half of the cancers overall and nearly one-third of the breast cancers were diagnosed before 30 years of age. These observations have important implications for asymptomatic carriers of germline p53 mutations, and there is a need for international collaboration in the development of protocols for the management of such families.
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PMID:Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. 811 19

Codon 257 of the p53 gene is an extremely rare target for somatic mutations (accounting for only two of 1600 published mutations). We report here two constitutional mutations both affecting the second nucleotide of codon 257. A thymine to adenine transversion resulting in an amino acid change from leucine to glutamine was found in one proband who developed multiple independent malignant tumors (osteosarcoma, phyllodes tumor, soft-tissue sarcoma). Her mother died of early-onset breast cancer. In the other case, a deletion resulting in a frameshift in the C-terminal coding region of p53 was found in a woman who was diagnosed with breast cancer at age 34. This woman belongs to a family with features of Li-Fraumeni syndrome. In both cases, the p53 mutations identified in the proband was found in other members of the family. Codon 257, even if rarely mutated in somatic cells, may thus be an important target for germ-line mutations.
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PMID:Two germ-line mutations affecting the same nucleotide at codon 257 of p53 gene, a rare site for mutations. 813 27

Distribution of miscarriages, stillbirths and infant deaths in the families of a population-based series of children with soft-tissue sarcoma was examined in relation to index case histology (rhabdomyosarcoma or other soft-tissue sarcoma) and to the possible presence of genetic predisposition to cancer in the families (Li-Fraumeni syndrome or neurofibromatosis). Reproductive loss was not related to index histology (miscarriages, p = 0.3; all losses, p = 0.6) but was significantly higher in "genetic" rather than "sporadic" families (miscarriages, p = 0.02; all losses, p = 0.01). However, excess reproductive loss was not a feature of families with the Li-Fraumeni syndrome, but appeared to be concentrated in the families affected by neurofibromatosis.
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PMID:Foetal loss and infant deaths in families of children with soft-tissue sarcoma. 831 40

Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder that predisposes individuals to multiple forms of cancer including breast carcinoma, soft tissue sarcoma, osteosarcoma, leukemia and adrenocortical carcinoma. These diverse tumor types develop at unusually early ages. Analysis of the tumor suppressor gene p53 in family members with LFS have demonstrated that germline mutations in the p53 gene were present in most of the LFS family tested so far. Furthermore, germline p53 mutations were also found in cancer-prone individuals which were not indicative of the LFS.
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PMID:Germline mutations of the p53 tumor-suppressor gene in cancer-prone families: a review. 851 Oct 38

Li-Fraumeni syndrome(LFS) is an autosomal dominant disorder that predisposes individuals to multiple forms of cancer including breast cancer, soft tissue sarcoma, brain tumor, osteosarcoma, leukemia, and adrenocortical carcinoma. Recently, germ-line mutation of the p53 tumor suppressor gene has been implicated in this familial disorder. We report a case of a 25-year old woman who presented with bilateral breast cancer and uterine leiomyoma. Her mother had died of early-onset bilateral breast cancer. And her younger sister had breast carcinoma as well, which was identified at the age of 22, indicating her strong familial history. To test for the presence of the p53 germ-line mutation, we analyzed the genomic DNA from the peripheral blood of the proband and her sister by PCR-SSCP analysis of exon 5 through exon 8 of the p53 gene. As a result, a p53 mutation in exon 7 was detected in an allele, and it was shared with her sister as the same pattern. Sequencing analysis determined the altered nucleotide at codon 248(CGG > TGG) which is one of the most frequent mutation sites related to LFS. Therefore, this patient has the most consistent characteristic features of LFS phenotype and it is believed that this case is the first report of a family with Li-Fraumeni syndrome carrying the p53 germ-line mutation in Korea.
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PMID:The first documentation of Li-Fraumeni syndrome in Korea. 852 48


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