PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Li-Fraumeni Syndrome”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed1994

Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1.

As normal cells progress toward malignancy, they must switch to an angiogenic phenotype to attract the nourishing vasculature that they depend on for their growth. In cultured fibroblasts from Li-Fraumeni patients, this switch was found to coincide with loss of the wild-type allele of the p53 tumor suppressor gene and to be the result of reduced expression of thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis. Transfection assays revealed that p53 can stimulate the endogenous TSP-1 gene and positively regulate TSP-1 promoter sequences. These data indicate that, in fibroblasts, wild-type p53 inhibits angiogenesis through regulation of TSP-1 synthesis.

Alleles↗
PubMed1992

p53 mutations in breast cancer.

We have identified and analyzed 41 mutations in p53 in sporadic breast tumors from 136 unselected breast cancer patients and estimate that approximately 40% of such tumors contain p53 mutations. The frequency of G-T transversions and the incidence of guanosine mutations in the nontranscribed strand of the p53 gene were found to be higher than expected, and we suggest, therefore, that exogenous carcinogens have an etiological role in sporadic breast cancers. Mutations were recorded in 44 codons of the p53 gene, with no obvious mutational hot-spots, although mutations at codons 175, 194, 273, and 280 accounted for 25% of the changes. One germ-line mutation was found in 136 patients and so we conclude that constitutional mutation of p53 may be an uncommon etiological factor in breast cancer.

Base Composition↗
PubMed1991

Tumorigenic transformation of spontaneously immortalized fibroblasts from patients with a familial cancer syndrome.

Immortal cell lines arose spontaneously during in vitro culture of initially normal fibroblasts, MDAH041 and MDAH087, from patients with Li-Fraumeni familial cancer syndrome. Fibroblasts from a control donor, MDAH170, maintained a normal morphology and senesced at 31 population doublings. The immortal fibroblasts have several properties of transformed cells. In addition to having acquired an altered morphology and chromosomal anomalies, MDAH041 and MDAH087 have escaped from senescence, growing beyond 300 and 100 population doublings (pd), respectively. As early as 50 pd, these cells can be transformed by an activated H-ras oncogene to form tumors in nude mice. However, MDAH041 immortal cells were resistant to tumorigenic transformation by transfection with the v-abl oncogene.

Animals↗
PubMed1991

Genetic epidemiology of childhood brain tumors.

The study goal was to determine the genetic (heritable) contribution to childhood brain tumors (CBT) which cause nearly one quarter of all childhood cancer deaths. Their etiology remains unknown, but previous studies have suggested a proportion of CBT may be heritable. In this study we collected family histories of 243 confirmed CBT patients referred to The University of Texas M. D. Anderson Cancer Center between the years 1944 and 1983, diagnosed before age 15, and residents of the United States or Canada. Family histories were obtained for all the probands' first degree relatives (parents, siblings, and offspring) and extended to include selected second degree relatives (aunts, uncles, grandparents) using sequential sampling. To determine if these CBT families exhibited excess cancer, we compared their cancer experience to age-, race-, sex-, and calendar-year specific rates from the Connecticut Tumor Registry. No cancer excess was observed among 1,099 first and second degree relatives [39 cancers observed (O) and 44 expected (E) for a standardized incidence ratio (SIR) of 0.88]. For colon cancer, although small numbers, five cases were observed among the probands' first degree relatives with 1.6 expected, for a significant SIR of 3.10. Segregation analysis demonstrated that chance alone could not account for the observed cancer distribution with a multifactorial model providing the best overall explanation of the data. Overall, heredity played a role in the etiology of CBT in 4% of the study families: four (1.7%) due to known hereditary syndromes (nevoid basal cell carcinoma syndrome and von Recklinghausens neurofibromatosis--NF-1), four (1.7%) with multifactorial inheritance, and two additional families with cancers aggregating similar to the clinical criteria described for the Li-Fraumeni cancer family syndrome.

Adolescent↗
PubMed1989

A review of astrocytoma in childhood.

Between 1954 and 1984, 282 children with astrocytoma were included in the Manchester Children's Tumour Registry (MCTR), giving an overall incidence of 9.3 per million person-years. There were 110 children with adult astrocytoma and 172 children with juvenile astrocytoma. The five-year survival for adult astrocytoma was 15% and 75% for juvenile astrocytoma. There were no significant improvements in survival with time. There were 21 children with neurofibromatosis (NF) and 4 children had tuberous sclerosis. Some children had other recognized syndromes and others had major or minor abnormalities. Nine children had second tumors, mainly associated with NF, and seven siblings had malignant tumors. A number of mothers of these children were found to have breast cancer. Some of these families may represent examples of the Li-Fraumeni cancer family syndrome. We conclude that astrocytomas is an important problem in childhood and that a proportion of cases may have a genetic origin.

Adolescent↗
PubMed1991

Cancer risk in second degree relatives of children with soft tissue sarcoma.

The risk of cancer in the second degree relatives of a population-based series of children with soft tissue sarcoma was studied in relation to (i) various characteristics in these relatives, (ii) certain clinical features in the index children previously identified as risk factors for cancer in their first degree relatives. Overall there was a non-significant deficit of cancers in the second degree relatives (RR = 0.88) and cancer risk was unrelated to type or site of cancer, type of relative, or to risk factors in the index case. The findings indicate that although the families investigated may include a proportion with the Li-Fraumeni cancer family syndrome, the increased cancer risk already reported in the first degree relatives does not extent to second degree relatives in general.

Adolescent↗
PubMed1992

A significant proportion of patients with osteosarcoma may belong to Li-Fraumeni cancer families.

We studied the pedigrees of 17 index patients with osteosarcoma, recording malignant disease and cause of death for first- and second-degree relatives. There were seven cancers and five cancer deaths per 2151.5 person-years in first-degree relatives of osteosarcoma patients under the age of 50 years, a significantly greater incidence than in an age- and sex-matched population group (p < 0.001). This excess of malignancy was largely due to two families which fulfilled the criteria for the Li-Fraumeni cancer family syndrome. Both of these families were shown to have the genetic alterations in the p53 gene which have been implicated in this syndrome. Our study suggests that orthopaedic surgeons seeing new cases of osteosarcoma should arrange screening for familial malignancy.

Adolescent↗
PubMed1992

Abnormal expression of wild type p53 protein in normal cells of a cancer family patient.

Mutations in the p53 gene are the commonest specific genetic change in human cancer. In normal tissues, p53 protein is present in such low quantities that it is not readily detectable by immunochemical techniques. However, in many tumour cells large amounts of p53 protein accumulate and can be seen by simple immunohistochemical staining; this is generally attributed to the accumulation of stabilised, mutant protein. We have found a mother and daughter, who both have a history of breast cancer, who show strong immunohistochemical staining of p53 in most of their normal epithelial and mesenchymal cells. Their family has a history of multiple cancers developing at an early age. Detailed protein analysis and gene sequencing of material obtained from cultured cells, grown from a skin biopsy taken from the daughter, suggest that her cells contained large quantities of normal (unmutated) p53. We suggest that this phenotype defines a new inherited cancer susceptibility syndrome that is distinct from the germ-line mutations in p53 found in some Li-Fraumeni families. This new syndrome affects p53 tumour suppressor function through an indirect mechanism that stabilises normal p53. It remains to be established whether this mechanism also contributes to the accumulation of p53 in sporadic cancers.

Adult↗