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

The Li-Fraumeni syndrome was initially recognized through clinical observations at the bed side, which was followed by epidemiological studies. Children suffering from rhabdomyosarcoma were shown to have two or more of six forms of cancer in their parents, grandparents and other relatives, indicating cancer family syndrome. This syndrome has been shown to involve tumor suppressor gene p53 mutations in the germ-line. The patients in the family most often have a proband with soft tissue sarcoma or osteosarcoma, and relatives with breast cancer, brain tumor, leukemia and adrenocortical cancer. Members of the family also appear to be at risk for developing second independent malignancies during their life span. Recommendations on predictive testing for germ line p53 mutations among cancer-prone individuals have been made by the subcommittees, which were sponsored by National Cancer Institute and the National Center for Human Genome Research.
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PMID:[Li-Fraumeni syndrome]. 853 47

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. Most mutations found are of missense type and located in the central region of the gene (exons 5 to 8). In the present study, a germline p53 alteration was identified in a late onset breast cancer family (kindred Lund 5; mean age 58 years) using single stranded conformation polymorphism and sequence analysis. The mutation (a CCG to CTG transition) at codon 82 in exon 4, resulting in a proline to leucine substitution, has not previously been reported and was not present in a control set of 60 healthy individuals. Three of five woman with breast cancer (45, 57 and 65 years) were carriers of the alteration. Loss of heterozygosity at the p53 locus was not seen in the primary tumors of these women, but appeared as a partial loss of the wildtype allele in subsequent recurrent lesions of two gene carriers. The family manifested no linkage to the p53 gene (a two-point LOD-score of -0.41), and has previously also been excluded for linkage to the BRCA1 and BRCA2 loci, as well as being carrier of a BRCA1 germline mutation. Although it seems unlikely that the p53 germline mutation is the major cause of disease predisposition in Lund 5, the data suggest that some p53 alteration may confer a subtle influence on breast cancer development and progression.
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PMID:A novel p53 germline alteration identified in a late onset breast cancer kindred. 871 Mar 80

We present an extended family with Li-Fraumeni syndrome characterised by gastric and breast carcinoma, glioma, sarcoma, and leukaemia. This family showed strong evidence of linkage to TP53, and three of four tumours analysed showed loss of the wild type allele. A codon 175 missense mutation was identified in exon 5 in all available affected subjects. Counselling, screening, and issues surrounding presymptomatic testing are discussed.
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PMID:An extended Li-Fraumeni kindred with gastric carcinoma and a codon 175 mutation in TP53. 882 20

The p53 gene is the most commonly altered gene in a multitude of human cancers. The alterations can be acquired somatically or transmitted through the germ-line. Bone and soft tissue sarcomas are frequently found to have acquired abnormalities in the p53 and mdm-2 genes. In soft tissue sarcoma, the amplification of the mdm-2 gene and the binding of its oncogene product to wild-type p53 protein functionally inactivates normal p53-regulated growth. Inherited mutations of the p53 gene are associated with the rare Li-Fraumeni familial cancer syndrome. Various tumor types arise in these families, with sarcomas of the bone and soft tissues and carcinoma of the breast being the most frequently observed. Transgenic mice with highly expressed mutated p53 have a higher incidence of tumors, including predominantly osteosarcomas and soft tissue sarcomas. In close similarity with the Li-Fraumeni syndrome, homozygously p53-null mice (transgenic mice carrying two non-functional p53 allele) are developmentally normal however they are susceptible to spontaneous tumor formation. This article reviews briefly the structure, function, and dysfunction of the p53 tumor-suppressor gene with particular focus on its role in the development of bone and soft tissue sarcoma.
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PMID:p53: functions, mutations and sarcomas. 905 90

Family history of cancer and features of the Li-Fraumeni syndrome (LFS) were investigated in 42 patients with soft tissue sarcoma or osteosarcoma in a pediatric hospital in Mexico City, and compared with 42 non-cancer children. Six subjects with cancer were found among 204 first-degree relatives of cancer patients while there were none among 183 first-degree relatives of non-cancer children. In three families, the proband had two affected relatives, and the type of neoplasia as well as the age of onset suggested the clinical diagnosis of LFS. Our results show that 7.1% of our pediatric patients with soft tissue sarcoma or osteosarcoma may belong to LFS families. The authors encourage pediatric and adult oncologists to pay more attention to the history of cancer in nuclear families for eventual hereditary cancer syndrome identification and cancer prevention.
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PMID:Li-Fraumeni syndrome in pediatric patients with soft tissue sarcoma or osteosarcoma. 929 35

Soft tissue sarcoma (STS) accounts for approximately 1% of all cancers diagnosed annually in the United States. Population-based data from Connecticut covering the years 1935-1989 have shown an increasing incidence of STS in both genders, with a greater increase among men than women. The recent increase in acquired immune deficiency syndrome-related Kaposi's sarcoma does not explain the upward trend in STS, dating back decades. Etiologic heterogeneity is suggested by epidemiologic variations that have been observed by subsite and cell type. Among the environmental factors associated with STS are external radiation therapy, Thorotrast, arsenical pesticides and medications, phenoxyherbicides, dioxin, vinyl chloride, immunosuppressive drugs, alkylating agents, androgen-anabolic steroids, human immunodeficiency virus, and human herpes virus type 8. In addition, STS occurs excessively among persons with certain heritable states including retinoblastoma, Li-Fraumeni syndrome, Gardner's syndrome, Werner's syndrome, nevoid basal cell carcinoma syndrome, neurofibromatosis type 1, and some immunodeficiency syndromes. These risk factors account for a minority of STS cases but provide leads for further epidemiologic and interdisciplinary studies into the genetic and environmental determinants of various forms of STS.
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PMID:The epidemiology of soft tissue sarcoma. 934 16

Rhabdomyosarcoma is the most common soft tissue sarcoma in children. Primary breast location has been reported rarely in the literature. Most rhabdomyosarcomas encountered in the breast more commonly are metastatic disease from some primary foci in another part of the body. This report addresses the case of an adolescent girl who had primary embryonal rhabdomyosarcoma of the breast with no evidence of local invasion or metastatic disease within the spectrum of Li-Fraumeni syndrome.
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PMID:Primary embryonal rhabdomyosarcoma of the breast in an adolescent female: a case report. 980 22

The hCHK2 gene encodes the human homolog of the yeast Cds1 and Rad53 G2 checkpoint kinases, whose activation in response to DNA damage prevents cellular entry into mitosis. Here, it is shown that heterozygous germ line mutations in hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in the TP53 gene. These observations suggest that hCHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and they also provide a link between the central role of p53 inactivation in human cancer and the well-defined G2 checkpoint in yeast.
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PMID:Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. 1063 95

Breast cancer is the most frequent tumor type among women in the United States and in individuals with Li-Fraumeni syndrome. The p53 tumor suppressor gene is altered in a large proportion of both spontaneous breast malignancies and Li-Fraumeni breast cancers. This suggests that loss of p53 can accelerate breast tumorigenesis, yet p53-deficient mice rarely develop mammary tumors. To evaluate the effect of p53 loss on mammary tumor formation, the p53(null) allele was back-crossed onto the BALB/c genetic background. Median survival was 15.4 weeks for BALB/c-p53(-/-) mice compared to 54 weeks for BALB/c-p53(+/-) mice. Sarcomas and lymphomas were the most frequent tumor types in BALB/c-p53(-/-) mice, whereas 55% of the female BALB/c-p53(+/-) mice developed mammary carcinomas. The mammary tumors were highly aneuploid, frequently lost the remaining wild-type p53 allele, but rarely lost BRCA1. Although mammary tumors were rarely detected in BALB/c-p53(-/-) female mice, when glands from BALB/c-p53(-/-) mice were transplanted into wild-type BALB/c hosts, 75% developed mammary tumors. The high rate of mammary tumor development in the BALB/c background, but not C57Bl/6 or 129/Sv, suggests a genetic predisposition toward mammary tumorigenesis. Therefore, the BALB/c-p53(+/-) mice provide a unique model for the study of breast cancer in Li-Fraumeni syndrome. These results demonstrate the critical role that the p53 tumor suppressor gene plays in preventing tumorigenesis in the mammary gland.
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PMID:Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice. A model for Li-Fraumeni syndrome. 1110 87

Li-Fraumeni syndrome (LFS) has been the most common terminology used for the syndrome. It is a rare familial dominantly inherited cancer syndrome characterized by a wide spectrum of neoplasms occurring in children and young adults. The canonical definition of LFS includes a proband diagnosed with sarcoma before 45 years of age, a first-degree relative with cancer before this same age and another first- or second-degree relative in the lineage with any cancer before this age or sarcoma at any age. Multiple studies have reported p53 germline mutations in LFS families in various parts of the world. As in sporadic tumors, loss of heterozygosity leading to the inactivation of the wild-type allele by deletion or mutation is observed in LFS tumors. Cancer-risk in mutation carriers has been estimated to be 73% in males and nearly 100% in females, the difference almost entirely explained by breast cancer. The identification of germline p53 mutations in rare cancer-prone families has given rise to the medical, counseling, psychological and ethical problems.
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PMID:The Li-Fraumeni syndrome. 1190 Aug 79


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