Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The eponym Li-Fraumeni syndrome is given to a particular form of cancer-prone family in which the main encountered tumors are sarcomas occurring in childhood and breast cancers affecting young adult females. There is also an increased frequency of cerebral tumors, leukemias and adrenal carcinomas among these families. The transmission of the cancer-proneness is autosomal dominant and related to the loss of function of the p53 tumor suppressor gene located on the short arm of the chromosome 17. The related p53 protein is identified but its precise mechanism of action and its regulation are still unclear. It seems to activate the genes which negatively regulate the multiplication of the cell and to act as a factor of transcription. A germline mutation of the p53 gene must be looked for in every cancer-prone family but also in case of multifocal tumors, particularly osteosarcomas and glioblastomas, and in case of second malignant neoplasm. This is of major scientific as well clinical interest. Indeed, the study of new families will help to better understand the molecular mechanisms underlying the syndrome. For the family itself this allow to identify the cancer prone members and to offer them preventive measures and early detection of cancers, particularly early breast cancer detection.
 ...
PMID:[Li-Fraumeni syndrome and germ-line mutations of the p53 gene]. 808 24

The isolation of genes that predispose to familial disease is an important goal in cancer research. The identification of such genes "opens up" the possibility of genetic diagnosis in families so that individuals who are at risk of cancer through inheriting a predisposing mutation can be identified. Genes that are involved in familial cancer syndromes may also be important in the pathogenesis of sporadic forms of the disease, which are often more common. In the search for genes that predispose to familial breast and ovarian cancer much recent progress has been made. A locus on the long arm of chromosome 17, in the interval 17q12-21, has been identified by genetic linkage, and appears to be responsible for disease in approximately 40% of breast cancer families and most families that contain breast and ovarian cancer. The region containing this locus, which has been called BRCA1, has been narrowed to a 3-4 cM interval defined by THRA1, the thyroid hormone receptor locus alpha, and D17S183, an anonymous microsatellite polymorphism. Loci other than BRCA1 that have been identified appear not only to predispose to breast and/or ovarian tumors, but to tumors at other sites too. A new locus has been identified on chromosome 2 which is linked to hereditary non-polyposis colorectal cancer (HNPCC). Families with HNPCC are also at risk of endometrial cancer and tumors of the ovary, amongst other cancer sites. Finally, mutations in the p53 gene are inherited in families with Li-Fraumeni syndrome, a rare cancer syndrome predisposing to breast tumors, sarcomas, leukemia and other cancers. Li-Fraumeni syndrome is also the only inherited cancer syndrome that predisposes at least in part to breast cancer where the actual predisposing gene is known. For the other cancer syndromes, the cloning of the predisposing genes is eagerly awaited.
 ...
PMID:Predisposing genes in breast and ovarian cancer: an overview. 811 68

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.
 ...
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.
 ...
PMID:Two germ-line mutations affecting the same nucleotide at codon 257 of p53 gene, a rare site for mutations. 813 27

Thirty-seven ovarian cancer-prone families have been identified through a French co-operative network. Three main clinical presentations were observed: site-specific ovarian cancer, breast/ovarian carcinoma syndrome and Lynch syndrome II. An additional kindred with features of Li-Fraumeni syndrome is reported. It is expected that a better understanding of the mechanisms of carcinogenesis will allow the development of new methods of screening and treatment. With this aim, recent studies have mapped the gene for early-onset familial breast cancer and breast/ovarian carcinoma syndrome to the same locus in the chromosome 17q12-q23 region. Results from linkage analysis of two breast/ovarian carcinoma families and three breast cancer families favour the hypothesis of genetic heterogeneity among breast and ovarian tumors.
 ...
PMID:Familial ovarian carcinoma: pedigree studies and preliminary results from linkage analysis. 817 63

Two genes predisposing females to autosomal dominant breast cancer are located on chromosome 17. Mutations in the p53-gene on the short arm have been shown to predispose females to early onset breast cancer in families with the rare Li-Fraumeni syndrome. Another locus on 17q (BRCA1), was found to be linked to the disease in a subset of families with breast cancer. In order to determine the involvement of tumour suppressor genes at these loci in tumour development, we studied allele losses for markers on chromosome 17 in 78 familial breast carcinomas. The analysis used six polymorphic DNA markers, three on each arm. We found support for at least four separate regions displaying allele losses on chromosome 17: the p53-region, the distal part of 17p, the BRCA1 region and the distal part of 17q. The frequency of allele losses on distal 17p (16%) is low in these familial tumours compared with the previously reported incidence in sporadic tumours (> 50%), whereas the frequency of losses at the p53 locus and on 17q was similar to sporadic tumours (5%-40%). These data suggest that several regions on chromosomal 17 can harbour tumour suppressor genes involved in tumour development of familial breast cancer.
 ...
PMID:Four separate regions on chromosome 17 show loss of heterozygosity in familial breast carcinomas. 845 89

In 1905, Parsons first described a family with a history of four generations with uveal melanoma associated with breast cancer. The family history has now been brought up to date using genealogical sources to determine the origin of this family which was traced to the East End of London in the early 19th century. In addition, immunohistochemical investigations have showed mutant p53, a tumor suppressor gene, in museum specimens of uveal melanoma after 150 years. This family probably represents the earliest example of the Li-Fraumeni syndrome on record.
 ...
PMID:Familial malignant melanoma of the uvea and p53: a Victorian detective story. 851 55

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.
 ...
PMID:The first documentation of Li-Fraumeni syndrome in Korea. 852 48

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.
 ...
PMID:[Li-Fraumeni syndrome]. 853 47

Oncogene is not categorized as a tumor marker in a strict sense, however, cancer related oncogens play an important role as a biomarker in hereditary malignant tumors in a wide sense. Various suppressor oncogenes have been identified in the autosomal dominant hereditary diseases such as APC, in familial adenomatous polyposis, p53 in Li-Fraumeni syndrome and BRACA 1 and 2 in breast cancer. By identifying the mutation site or deletions of germ line, it is possible to make a presymptomatic diagnosis of those hereditary malignant tumors. There is splendid progress in understanding of DNA repair mechanism. Recently, the mismatch repair genes were cloned as a causing gene of HNPCC. There are another group of genes called nucleotide excision repair genes which are causative genes of various autosomal recessive hereditary diseases such as xeroderama pigmentation. Pro and cons of presymptomatic diagnosis of familial adenomatous polyposis were discussed in a series of 72 patients among 42 family trees.
 ...
PMID:[Role of tumor marker in the presymptomatic diagnosis of hereditary malignant tumors]. 869 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>