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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Germ line mutations in the tumor suppressor gene, p53, are known to cause Li-Fraumeni syndrome (LFS) or Li-Fraumeni-like syndrome (LFL). We sought to identify p53 germ line mutations in potential hereditary breast cancer patients without LFS/LFL phenotype, which will help us establish the genetic testing strategy for p53 in Chinese high-risk breast cancer families. We screened all coding exons and intron-exon boundaries of p53 in 240 women with early-onset breast cancer or affected relatives from four breast disease clinical centers in China by utilizing PCR-DHPLC and DNA sequencing analysis. Additionally, three cell lines (H1299, MCF-7, and MDA-MB-231) were transfected with pEGFP-N1-only or pEGFP-N1 vectors expressing either wild-type or two novel identified mutant p53. And then we performed flow cytometry analysis in the transfected cells to determine the status of cell apoptosis, and real-time PCR as well as western blot analysis to ascertain the expression of p53, p21, and p27. Two novel germ line mutations (563T > C and 643_660del18) were detected in two independent families. Neither of them, however, was present in the 768 normal controls. Functional assays revealed that the ability to trigger cell apoptosis and transcriptional activation of target gene under similar expression of p53 were lower in two mutants versus wild-type p53. Deleterious mutations of p53 seemed to be responsible for approximately 1% of non-BRCA1/BRCA2 hereditary breast cancer in Chinese population, and our findings suggested that p53 should be included in genetic testing of Chinese non-LFS/non-LFL high-risk breast cancer families.
Breast Cancer Res Treat 2010 Jan
PMID:Identification and characterization of two novel germ line p53 mutations in the non-LFS/non-LFL breast cancer families in Chinese population. 1923 35

Germ-line mutations in the TP53 gene are rare, but predispose women to a range of cancer types, including early-onset breast cancer. Breast cancers in women from families with the Li-Fraumeni syndrome often occur before age 30. The prevalence of deleterious TP53 mutations in unselected women with early-onset breast cancer is not precisely known. If mutations were found to be sufficiently common, it might be prudent to offer genetic testing to affected women in this age group. We screened the entire TP53 gene in the germ-line DNA from 95 women of various ethnic groups who were diagnosed with breast cancer before age 30, and who had previously been found to be negative for BRCA1 and BRCA2 mutations. No TP53 mutation was found. This study does not support a policy that TP53 testing should be offered routinely to unselected women with early-onset breast cancer in the absence of a family history of cancer.
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PMID:The prevalence of germ-line TP53 mutations in women diagnosed with breast cancer before age 30. 1971 88

Magnetic resonance imaging is a major component of breast imaging. Many studies have shown that magnetic resonance imaging is the most sensitive imaging method for detecting invasive breast cancer in comparison with mammography, ultrasound, and clinical breast examinations. Evidence-based clinical indications for breast magnetic resonance imaging include screening patients at high risk for breast cancer, including those with breast/ovarian cancer genes (BRCA1 and BRCA2), those who are untested first-degree relatives of carriers of these genes, those whose lifetime risk of developing breast cancer is 20% to 25% or greater, those who had chest radiation when they were 10 to 30 years old, and those who have or are first-degree relatives of people with Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome. Breast magnetic resonance imaging is performed in conjunction with mammography and does not replace mammography. Outside of the screening population, utilization of breast magnetic resonance imaging for newly diagnosed breast cancer patients and its use as a problem-solving technique for equivocal mammographic or clinical findings remain controversial. An understanding of the current evidence facilitates appropriate utilization of this important medical resource. This article discusses indications for ordering breast magnetic resonance imaging and how to read the breast magnetic resonance imaging report and understand the lexicon used.
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PMID:Breast magnetic resonance imaging: an overview for nonradiologists. 2001 26

Distinguishing a lymphadenopathy from neck swelling due to other causes may not be easy in children. The authors describe a case of an 18-month-old child who presented with unilateral partoid swelling, which was subsequently diagnosed as embryonal rhabdomysarcoma. Because of a family history of breast cancer and the association between breast cancer in a family and rhabdomyosarcoma, Li-Fraumeni syndrome, a more aggressive approach to diagnosis was pursued.
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PMID:Li-Fraumeni syndrome - What does it mean for the general practitioner and general paediatrician? 2040 Dec 24

Mutations of the sequence-specific master regulator p53 that alter transactivation function from promoter response elements (RE) could result in changes in the strength of gene activation or spectra of genes regulated. Such mutations in this tumor suppressor might lead to dramatic phenotypic changes and diversification of cell responses to stress. We have determined "functional fingerprints" of sporadic breast cancer-related p53 mutants, many of which are also associated with familial cancer proneness such as the Li-Fraumeni syndrome and germline BRCA1/2 mutant-associated cancers. The ability of p53, wild-type and mutants, to transactivate from 11 human target REs has been assessed at variable expression levels using a cellular, isogenomic yeast model system that allows for the rapid analysis of p53 function using a qualitative and a quantitative reporter. Among 50 missense mutants, 29 were classified as loss of function. The remaining 21 retained transactivation toward at least one RE. At high levels of galactose-induced p53 expression, 12 of 21 mutants that retain transactivation seemed similar to wild-type. When the level of galactose was reduced, transactivation defects could be revealed, suggesting that some breast cancer-related mutants can have subtle changes in transcription. These findings have been compared with clinical data from an ongoing neoadjuvant chemotherapy treatment trial for locally advanced breast tumors. The functional and nonfunctional missense mutations may distinguish tumors in terms of demographics, appearance, and relapse, implying that heterogeneity in the functionality of specific p53 mutations could affect clinical behavior and outcome.
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PMID:Altered-function p53 missense mutations identified in breast cancers can have subtle effects on transactivation. 2040 15

BACKGROUND Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome. Most families fulfilling the classical diagnostic criteria harbour TP53 germline mutations. However, TP53 germline mutations may also occur in less obvious phenotypes. As a result, different criteria are in use to decide which patients qualify for TP53 mutation analysis, including the LFS, Li-Fraumeni-like (LFL) and Chompret criteria. We investigated which criteria for TP53 mutation analysis resulted in the highest mutation detection rate and sensitivity in Dutch families. We describe the tumour spectrum in TP53-positive families and calculated tumour type specific relative risks. METHOD A total of 180 Dutch families referred for TP53 mutation analysis were evaluated. Tumour phenotypes were verified by pathology reports or clinical records. RESULTS A TP53 germline mutation was identified in 24 families. When the Chompret criteria were used 22/24 mutations were detected (sensitivity 92%, mutation detection rate 21%). In LFS and LFL families 18/24 mutations were found (sensitivity 75%). The two mutations detected outside the 'Chompret group' were found in a child with rhabdomyosarcoma and a young woman with breast cancer. In the mutation carriers, in addition to the classical LFS tumour types, colon and pancreatic cancer were also found significantly more often than in the general population. CONCLUSION We suggest TP53 mutation testing for all families fulfilling the Chompret criteria. In addition, TP53 mutation testing can be considered in the event of childhood sarcoma and breast cancer before 30 years. In addition to the risk for established LFS tumour types, TP53-positive individuals may also have an elevated risk for pancreatic and colon cancer.
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PMID:TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. 2052 32

Extract: A single inherited mutant gene may be enough to cause a very high cancer risk. Single-mutation cases have provided much insight into the genetic basis of carcinogenesis, but they are relatively rare and account for only a small fraction of all cancers. Examples include mutation to the APC gene, causing early onset colon cancer in the syndrome familial adenomatous polyposis (tumorous polyp-tissue in the colon); mutation to either the BRCA1 or BRCA2 genes, causing an increased risk of breast cancer; and mutation to the TP53 gene, causing Li-Fraumeni syndrome with various early onset cancers such as bone or soft tissue sarcoma. Cancers sometimes cluster in families, but do not follow the rigid inheritance pattern characteristic of a mutation to a single gene. Males with a brother or father who has suffered prostate cancer are more likely to develop the disease. Similarly, females with a sister or mother who has suffered breast cancer are more likely to get a breast tumor. Some of the clustering may arise from the common diet and environment shared by families. Recently, however, researchers have begun to assign a significant fraction of cancer risk to the particular genetic variants that individuals inherit.
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PMID:Inheritance of cancer. 2070 38

A small, but important, percentage of breast cancer cases is caused by the inheritance of a single copy of a mutated gene. BRCA1 and BRCA2 are the genes most commonly associated with inherited breast cancer; however, mutations in TP53 and PTEN cause Li-Fraumeni syndrome and Cowden syndrome, respectively, both of which are associated with high lifetime risks of breast cancer. Advances in the field of breast cancer genetics have led to an improved understanding of detection and prevention strategies. More recently, strategies to target the underlying genetic defects in BRCA1- and BRCA2-associated breast and ovarian cancers are emerging and may have implications for certain types of sporadic breast cancer.
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PMID:Breast cancer predisposition syndromes. 2081 75

CHEK2 gene mutations occur in a subset of patients with familial breast cancer, acting as moderate/low penetrance cancer susceptibility alleles. Although CHEK2 is no longer recognized as a major determinant of the Li-Fraumeni syndrome, a hereditary condition predisposing to cancer at multiple sites, it cannot be ruled out that mutations of this gene play a role in malignancies arising in peculiar multi-cancer families. To assess the contribution of CHEK2 to the breast cancer/sarcoma phenotype, we screened for germ-line sequence variations of the gene among 12 probands from hereditary breast/ovarian cancer families with one case of sarcoma that tested wild-type for mutations in the BRCA1, BRCA2, and TP53 genes. Two cases harbored previously unreported mutations in CHEK2, the c.507delT and c.38A>G, leading to protein truncation (p.Phe169LeufsX2) and amino acid substitution (p.His13Arg), respectively. These mutations were not considered common polymorphic variants, as they were undetected in 230 healthy controls of the same ethnic origin. While the c.38A>G encodes a mutant protein that behaves in biochemical assays as the wild-type form, the c.507delT is a loss-of-function mutation. The identification of two previously unreported CHEK2 variants, including a truncating mutation leading to constitutional haploinsufficiency, in individuals belonging to families selected for breast cancer/sarcoma phenotype, supports the hypothesis that the CHEK2 gene may act as a factor contributing to individual tumor development in peculiar familial backgrounds.
Breast Cancer Res Treat 2011 Nov
PMID:Two new CHEK2 germ-line variants detected in breast cancer/sarcoma families negative for BRCA1, BRCA2, and TP53 gene mutations. 2156 11

Mutations of the p53 suppressor -ene are the most common genetic lesion noted in human cancers and appear to be relatively common (30%) as somatic cell mutations in female breast cancer. p53 mutations have also been frequently reported in familial breast cancers as in Li-Fraumeni syndrome (LFS). Males with breast cancer are far rarer than females. We investigated the mutational spectra of the p53 gene in male breast cancers. Of 10 samples analyzed for p53 mutations in exons 5, 6. 7 and 8, only two showed point mutations corresponding to amino acid residues 248 and 290. One of the point mutations turned out to be a silent change, thus representing only DNA polymorphism. Although the number of male breast cancer samples thus far examined is small, the p53 mutations in male breast cancer (10%), unlike females (30%), does not appear to be as frequent.
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PMID:Relative paucity of p53 gene-mutations in male breast carcinomas. 2157 18


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