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

The determination of the physical map of human chromosome 11 will require more clones than are currently available. We have isolated an additional 1001 new markers in a bacteriophage vector from a somatic cell hybrid cell line that contains most of chromosome 11, except the middle of the short arm. These markers were localized to five different regions, 11p15-pter, 11p12-cen, 11q11-q14, 11q14-q23, and 11q23-qter, by a panel of previously characterized somatic cell hybrids. The region 11q11-14 harbors genes that have been shown to be important in breast cancer, B-cell lymphomas, centrocytic lymphomas, asthma, and multiple endocrine neoplasia, type 1 (MEN1). To determine the positions of the recombinant clones located there, we developed a new series of radiation-reduced somatic cell hybrids. These hybrids, together with those previously characterized, allowed us to map the 11q11-q14 markers into 11 separate segregation groups.
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PMID:Isolation of 1001 new markers from human chromosome 11, excluding the region of 11p13-p15.5, and their sublocalization by a new series of radiation-reduced somatic cell hybrids. 135 39

Cancer is genetic, in the sense that it is caused by DNA alterations at the cellular level. On the other hand, the most important risk factors for the common cancers are environmental: cigarette smoking, environmental pollution, occupational exposures, poor diet, and so on. These two observations are not in conflict: the DNA alterations that lead to cancer are very likely to be caused by environmental mutagens. It would be valuable to know exactly what genes are altered to cause a specific cancer, because the effects of these alterations might then be reversible before cancer has a chance to develop. A key to identifying these cancer genes may lie with rare families at extremely high risk of a specific cancer. Unlike most cancer patients, members of these families may inherit an alteration that confers increased susceptibility to cancer. In these rare instances, cancer is a genetic disease at the level of the family, as well as at the level of the cell. Therefore, in these families, genes predisposing to cancer can be mapped in the same way as genes for purely genetic diseases like sickle cell anaemia, cystic fibrosis, and Huntington's disease. The hypothesis that underlies the mapping of cancer genes in families is that the genes inherited in altered form in these rare families are the same genes that are altered in somatic cells of individuals without a remarkable family history of cancer. This hypothesis has proved correct for retinoblastoma. Genes responsible for other rare cancers have been mapped in families as well: neurofibromatosis, multiple endocrine neoplasia, Wilms' tumour, and colon cancer following familial adenomatous polyps, among others. Genes responsible for common cancers are also being defined by genetic analysis, most notably breast cancer and colon cancer. This review summarizes why, how, and what genetic analysis of families can reveal about human cancers.
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PMID:Genetic analysis of cancer in families. 210 20

Most cancers appear to be sporadic. However, 5 to 10% of cancers occur in genetically predisposed individuals. This inherited genetic risk is observed in syndromes such as familial polyendocrinopathies or phacomatosis such as neurofibromatosis, but also in familial aggregations of frequent cancers such as breast or colon cancers. Thanks to studies on molecular genetics, it has been possible over the last ten years to localize and to identify a large number of predisposing genes. These discoveries have permitted to better understand the biological basis of the predisposition and to offer counselling by identifying at-risk individuals in those families. In the case of multiple endocrine neoplasia type 2 associated with an elevated risk for medullary thyroid cancer, the gene involved is a protooncogene named RET and located on chromosome 10. Point mutations affecting specific regions of this gene are the basis of the genetic predisposition. For familial breast cancer, a susceptibility gene named BRCA1 has been located on the long arm of chromosome 17. Mutation of this gene (yet to be identified) led to very elevated risk of breast cancer and also in some families of ovarian cancer.
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PMID:[Genetic predisposition to cancer: familial forms of medullary thyroid cancer and breast cancer]. 803 90

We investigated the prevalence of Gs alpha gene mutations in growth hormone (GH) secreting pituitary adenomas from Japanese patients with acromegaly. Forty-five GH-secreting adenomas were examined for the presence of point mutations in codons 201 or 227 of the Gs alpha gene using the polymerase chain reaction-direct sequencing method and deoxyribonucleic acid extracted from paraffin-embedded tumor specimens. Mutation of codon 227 of the Gs alpha gene was not observed in any of the tumors, but a mis-sense mutation of codon 201 was identified in two tumors (4.4%). One lesion was a densely granulated GH cell adenoma in a patient with adenomatous goiter and breast cancer. The other was a mixed GH cell-prolactin cell adenoma in a patient with multiple endocrine neoplasia type 1 associated with parathyroid hyperplasia and a pancreatic islet cell tumor. The Gs alpha gene detected in parathyroid tissue and pancreatic tumor tissue was of the wild type in this second patient, and the mutation was specific to the pituitary tumor. These results suggest that point mutations of codons 201 or 227 of the Gs alpha gene may not be important mediators of oncogenesis for GH-secreting pituitary adenomas in Japan.
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PMID:Analysis of the Gs alpha gene in growth hormone-secreting pituitary adenomas by the polymerase chain reaction-direct sequencing method using paraffin-embedded tissues. 823 46

The recent remarkable progress in molecular biology has revealed that various kinds of genetic alteration occur in cancers. Recently, many genes that cause hereditary cancer have been identified. For example, hMSH2 and hMLH1, which are known as DNA mismatch repair genes have been found to cause HNPCC (hereditary non-poliposis colorectal cancer). Mutation of RET oncogene has been recognized in the families of MEN (multiple endocrine neoplasia) type II. Mutations of the tumor suppressor genes are the most common changes in the genes of familial cancer. BRCA1 and BRCA2 are tumor suppressor genes that have recently been identified as familial breast and ovarian cancer, familial breast cancer genes. This paper reviewed the hereditary cancer families in which genetic alterations have been revealed and the recent progress in mapping and cloning of familial breast cancer candidate genes which have not been identified.
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PMID:[Familial cancer and oncogenic factors]. 867 87

The role of primary genetic factors in the etiology of cancer has become of intense interest to the research and clinical community. This interest has been heightened by recent discoveries that germ-line mutations such as BRCA1 and BRCA2 in hereditary breast cancer are responsible for an increasing percentage of common solid tumors. A potpourri of proto-oncogenes and tumor-suppressor genes has been identified in hereditary as well as certain common sporadic and rare cancer types, and new cancer genes will likely be discovered every month to account for the 5 to 10% of the cases of cancer that can be attributed to primary genetic factors. Molecular mechanisms in the pathogenesis of hereditary cancer can result in more-targeted cancer-control measures. At least four mutator genes (MHS2, MLH1, PMS1 and PMS2) appear to account for 70-80% of hereditary nonpolypoid colorectal cancer (HNPCC). When one of these germ-line mutations is present in an HNPCC family, the physician is then able to determine the patient's lifetime cancer destiny with an accuracy of about 90% (limited only by the penetrance of the gene). This will enable highly targeted surveillance to be initiated early, such as colonoscopy beginning at ages 20 to 25 or prophylactic subtotal colectomy. Also, in multiple endocrine neoplasia syndromes (MEN 2A and 2B), the identification of the culprit RET proto-oncogene now enables a secure diagnosis and permits testing of children who might benefit from prophylactic total thyroidectomy. Central to translation of these momentous molecular genetic discoveries into patient care is the necessity of determining who requires DNA testing. The cancer family history is the linchpin in making this decision.
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PMID:Cancer genetics in the new era of molecular biology. 961 36

Genetic testing has been widely available and useful in several kinds of familial cancer. Shinshu University Hospital established a division of clinical and molecular genetics as one of its central service departments. We have a staff meeting once a week to discuss each case to provide the suitable counseling and the ethical-legal and social issues. We performed genetic testing in 44 cases, including familial adenomatous polyposis, multiple endocrine neoplasia type 1 and 2, familial breast cancer, von Hippel-Lindau disease, and Li-Fraumeni syndrome. This is the first clinical genetics department in the National University Hospitals in Japan and this system increases the utility of genetic testing.
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PMID:[Hereditary cancer and genetic testing: the role of division of clinical and molecular genetics]. 1087 51

The racemate compound MEN 11066 (1-[(benzofuran-2-yl)(4'-cyanophenyl)methyl]-1H-1,2,4-triazole) and its enantiomers, (+)-MEN 11623 and (-)-MEN 11622, showed potent and selective aromatase activity on human placental microsomes. In addition, to better evaluate their potency as anticancer drugs, the compounds were assayed on testosterone-induced cell proliferation to measure their ability in inhibiting oestrogen-dependent tumour growth. Two different sublines originated from the human breast carcinoma MCF-7 were used. One, named MCF-7(tumour aromatase) (TA), that had maintained its intrinsic aromatase activity, was more sensitive to estradiol or testosterone-induced growth than the second subline named MCF-7(human placental aromatase) (hPA). The latter had been transfected with the human placental aromatase cDNA, after recognizing that the parental cells had aromatase activity reduced to undetectable levels. The MEN compounds completely reverted the testosterone-induced proliferation in both MCF-7(TA) and MCF-7(hPA) cells, while they did not affect the estradiol-triggered proliferation as a proof of their specificity for aromatase enzyme. Interestingly, MCF-7(TA) cells were more susceptible to the effects of aromatase inhibitors than the MCF-7(hPA) cell. These data suggest the efficacy of aromatase inhibitors in breast cancer when the growth dependency from oestrogen is high and a relatively low aromatase activity may be extremely important for tumour development.
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PMID:Effect of the aromatase inhibitor, MEN 11066, on growth of two different MCF-7 sublines. 1110 22

Clinical cancer genetics is becoming an integral part of the care of cancer patients. This review describes the clinical aspects, genetics, and clinical genetic management of most of the major hereditary cancer susceptibility syndromes. Multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and familial adenomatous polyposis are examples of syndromes for which genetic testing to identify at-risk family members is considered the standard of care. Genetic testing for these syndromes is sensitive and affordable, and it will change medical management. Cancer genetic counseling and testing is probably beneficial in other syndromes, such as the hereditary breast cancer syndromes, hereditary nonpolyposis colorectal cancer syndrome, Peutz-Jeghers syndrome, and juvenile polyposis. There are also hereditary cancer syndromes for which testing is not yet available and/or is unlikely to change medical management, including Li-Fraumeni syndrome and hereditary malignant melanoma. Thorough medical care requires the identification of families likely to have a hereditary cancer susceptibility syndrome for referral to cancer genetics professionals.
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PMID:Genetic testing for cancer predisposition. 1116 Jul 85

The current model of human neoplasia invokes a number of potential genomic alterations that impact cellular phenotype and proliferative rates. In the majority of human tumor models, the transformation from normal cells to neoplastic lesion is a multistep process. This review offers a specific overview of the involvement of tumor suppressor genes (TSGs) in the pathogenesis of human pituitary adenomas. TSG genetic lesions, such as BRCA1 in breast cancer and p53 in Li-Fraumeni Syndrome, have been identified in both sporadic and heritable human endocrine tumors. Familial neoplastic syndromes like multiple endocrine neoplasia type 1 (MEN1) that include pituitary tumor formation as part of a broad clinical spectrum of disease represent a unique opportunity to investigate the general mechanisms of tumorigenesis, and well as genes responsible for sporadic endocrine tumors. Similarly, homologous recombination knockout mice with selectively ablated candidate TSGs have also shed light on the molecular mechanisms of pituitary cell proliferation and tumor suppression. However, despite insights into pituitary tumorigenesis generated by heritable neoplasia syndromes and mouse knockout of critical TSGs that display a pituitary tumor phenotype, the molecular pathogenesis of human pituitary adenomas remains largely an enigma. Thus, the role of TSGs, if any, in sporadic pituitary adenoma formation has yet to be determined, despite our greater understanding of the molecular mechanisms underlying pituitary cell function and phenotype.
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PMID:Tumor suppressor loss in pituitary tumors. 1141 76


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