Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently demonstrated a high frequency of loss of heterozygosity (LOH) at the D17S856 and D17S855 (within the BRCA1 gene) loci in primary prostate cancer, suggesting that the BRCA1 gene and/or other tumor suppressor gene(s) located within the interval of the D17S856 and D17S855 loci and/or within the vicinity of this interval may be important in prostate cancer (Cancer Res., 55: 1002-1005, 1995). To further define the exact boundary of the deleted region (i.e., D17S856/D17S855) and to detect other possible LOH regions on the long arm of chromosome 17, we analysed 23 matched normal and tumor DNAs with 15 polymorphic microsatellite markers spanning chromosome 17q12-21. Eleven of 22 (50%) informative tumors showed allelic deletion at one or more of the loci studied. A minimal area of LOH was identified to extend from the proximal boundary at the D17S776 locus to the distal boundary at the D17S855 locus, spanning an estimated < 2 Mb segment on chromosome 17q21. Our results suggest that a potential tumor suppressor gene(s) may reside in the < 2 Mb region centromeric (inclusive) to the BRCA1 gene and that this tumor suppressor gene(s) may be involved in the formation of prostate cancer.
 ...
PMID:Localization of potential tumor suppressor loci to a < 2 Mb region on chromosome 17q in human prostate cancer. 747 43

Genetic epidemiological evidence suggests that mutations in BRCA1 may be responsible for approximately one half of early onset familial breast cancer and the majority of familial breast/ovarian cancer. The recent cloning of BRCA1 allows for the direct detection of mutations, but the feasibility of presymptomatic screening for cancer susceptibility is unknown. We analyzed genomic DNA from one affected individual from each of 24 families with at least three cases of ovarian or breast cancer, using SSCP assays. Variant SSCP bands were subcloned and sequenced. Allele-specific oligonucleotide hybridization was used to verify sequence changes and to screen DNA from control individuals. Six frameshift and two missense mutations were detected in 10 different families. A frameshift mutation was detected in a male proband affected with both breast and prostate cancer. A 40-bp deletion was detected in a patient who developed intra-abdominal carcinomatosis 1 year after prophylactic oophorectomy. Mutations were detected throughout the gene, and only one was detected in more than a single family. These results provide further evidence that inherited breast and ovarian cancer can occur as a consequence of a wide array of BRCA1 mutations. These results suggests that development of a screening test for BRCA1 mutations will be technically challenging. The finding of a mutation in a family with male breast cancer, not previously thought to be related to BRCA1, also illustrates the potential difficulties of genetic counseling for individuals known to carry mutations.
 ...
PMID:Detection of eight BRCA1 mutations in 10 breast/ovarian cancer families, including 1 family with male breast cancer. 761 Dec 77

Recent evidence obtained by in situ hybridization indicates that chromosomal region 17q is often lost in prostate tumors. To substantiate the presence of tumor suppressor genes in this chromosomal region, normal human 17q tagged with a neomycin resistance gene was transferred into a human prostate cancer cell line, PPC-1, by microcell-mediated chromosome transfer. Two hybrid clones were obtained, both of which showed decreased tumorigenicity in athymic nude mice and decreased efficiency of colony formation in soft agar with respect to PPC-1. When microcells were irradiated prior to transfer of chromosomal region 17q to determine which subchromosomal regions carry the potential tumor suppressor gene(s), 10 hybrid clones were obtained, including 6 fully malignant and 4 suppressed clones. Analysis of polymorphic loci on 17q in the series of hybrid clones suggested that a tumor suppressor gene associated with prostate cancer was located in a region no more than 28 cM long at 17q12-q22, which includes the BRCA1 gene involved in hereditary breast cancer.
 ...
PMID:Suppression of malignant phenotype in a human prostate cancer cell line by fragments of normal chromosomal region 17q. 761 77

A putative tumor suppressor gene, the BRCA1 gene, on chromosome 17q21 has recently been identified and shown to be mutated in breast and ovarian cancers. We have undertaken the present study to explore the possible involvement of the BRCA1 and/or other potential genes on chromosome 17q in prostate cancer. Twenty-three patients were screened by PCR for loss of heterozygosity at five microsatellite loci spanning the region of 17q12-21. One of the loci (i.e., D17S855) studied is intragenic to the BRCA1. Forty-four and 40% of the informative cases showed loss of heterozygosity at the BRCA1 (D17S855) and D17S856 loci, respectively, whereas 10%, 10%, and 11% of the informative cases were positive for loss of heterozygosity at the D17S250, D17S579, and D17S588 loci, respectively. Overall, 52% (11/21) of the informative cases have allelic loss of at least one locus on chromosome 17q. Our data suggest that the BRCA1 and/or other genes within the interval between BRCA1 and D17S856 on 17q21 may be important in the pathogenesis of prostate cancer.
 ...
PMID:Loss of heterozygosity of the BRCA1 and other loci on chromosome 17q in human prostate cancer. 786 81

Germline mutations in a gene on chromosome 17q known as BRCA1 are responsible for a large proportion of inherited predispositions to breast and ovarian cancer. In 33 families with evidence of linkage to BRCA1, we estimated the risks of breast and ovarian cancer from the occurrence of second cancers in individuals with breast cancer, and examined the risks of other cancers in BRCA1 carriers. 26 contralateral primary breast cancers occurring more than 3 years after a first breast cancer were observed before age 70, giving an estimated cumulative risk of breast cancer in gene carriers of 87% by age 70.23 primary ovarian cancers occurred in women with a previous breast cancer, resulting in an estimated cumulative risk of ovarian cancer of 44% by age 70.87 cancers other than breast or ovarian cancer were observed in individuals with breast or ovarian cancer and their first-degree relatives compared with 69.3 expected, based on national incidence rates. Significant excesses were observed for colon cancer (estimated relative risk [RR] to gene carriers 4.11 [95% CI 2.36-7.15]) and prostate cancer (3.33 [1.78-6.20]). No significant excesses (or deficits) were noted for cancers of other sites. Our study provides estimates of breast and ovarian cancer risks which are useful for counselling BRCA1-mutation carriers. It also shows that carriers are at increased risk of colon and prostate cancer, which may be of clinical significance in certain families if the risks are associated with specific mutations.
 ...
PMID:Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. 790 78

Thirty-seven families with four or more cases of breast cancer or breast and ovarian cancer were analyzed for mutations in BRCA1. Twelve different germ-line mutations, four novel and eight previously observed, were detected in 16 families. Five families of Ashkenazi Jewish descent carried the 185delAG mutation and shared the same haplotype at eight polymorphic markers spanning approximately 850 kb at BRCA1. Expressivity of 185delAG in these families varied, from early-onset breast cancer without ovarian cancer. Mutation 4184delTCAA occurred independently in two families. In one family, penetrance was complete, with females developing early-onset breast cancer or ovarian cancer and the male carrier developing prostatic cancer, whereas, in the other family, penetrance was incomplete and only breast cancer occurred, diagnosed at ages 38-81 years. Two novel nonsense mutations led to the loss of mutant BRCA1 transcript in families with 10 and 6 cases of early-onset breast cancer and ovarian cancer. A 665-nt segment of the BRCA1 3'-UTR and 1.3 kb of genomic sequence including the putative promoter region were invariant by single-strand conformation analysis in 13 families without coding-sequence mutations. Overall in our series, BRCA1 mutations have been detected in 26 families: 16 with positive BRCA1 lod scores, 7 with negative lod scores (reflecting multiple sporadic breast cancers), and 3 not tested for linkage. Three other families have positive lod scores for linkage to BRCA2, but 13 families without detected BRCA1 mutations have negative lod scores for both BRCA1 and BRCA2.
 ...
PMID:Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families. 853 57

Japanese breast cancer families were collected and classified into the following 7 types according to the onset age and the distribution of other cancers in the family lines; early-onset type, late-onset type, familial breast-ovarian cancer type, familial breast-prostate cancer type, familial breast-thyroid cancer type, familial male and female breast cancer type and multiple primary cancer type. We have detected no p53 germ line mutations in the patients from these families. Linkage with BRCA1 was not detected in any single families. These data indicate that neither BRCA1 or p53 is a major susceptible gene in Japanese familial breast cancer. However, in the two site-specific breast cancer families, the same nonsense mutation of the BRCA1 gene was detected.
 ...
PMID:[Familial breast cancer]. 853 41

BRCA1 is a breast cancer-related tumor suppressor gene located on human chromosome 17q21. Inherited mutations in BRCA1 are thought to be responsible for approximately half of all inherited breast cancer and to confer increased risk for ovarian, colon, or prostate cancer. Studies of affected families and population-based studies have provided some information on the prevalence of BRCA1 mutations in Caucasian U.S. and European populations as well as on the penetrance of these mutations. We review the available data on the epidemiology of breast cancer with specific reference to BRCA1. In addition, we describe the genetic analysis of one large family with multiple affected individuals now known to harbor a BRCA1 germline mutation but initially identified by genetic linkage analysis. This family is presented as a model of the challenges that can be encountered in genetic analysis of familial forms of cancer. To this end, we compare the outcome of analysis before and after the identification of a mutation that predisposes family members to early-onset breast and ovarian cancers. We describe seven additional families with evidence of linkage between breast cancer and genetic markers in the BRCA1 region. Each of these families generated a 2-point LOD (i.e., logarithm of the odds) score greater than 1.18 for at least one polymorphic marker flanking BRCA1. These families have formed the basis of our efforts to characterize BRCA1 mutations. First-pass mutation analysis using the single-strand conformation polymorphism approach failed to identify any mutations in the seven families. We consider the possible reasons for the apparent low mutation-detection efficiency.
 ...
PMID:Genetic analysis of eight breast-ovarian cancer families with suspected BRCA1 mutations. 857 62

The breast cancer susceptibility gene BRCA2 on chromosome 13q12-13 has recently been identified. Germline mutations of BRCA2 are predicted to account for approximately 35% of families with multiple case, early onset female breast cancer, and they are also associated with an increased risk of male breast cancer, ovarian cancer, prostate cancer and pancreatic cancer. Germline mutations of a second cancer susceptibility gene BRCA1 (ref. 5), are associated with a strong predisposition to ovarian cancer as well as female breast cancer. Recent studies have suggested that the phenotype in BRCA1 families with respect to the ratio of breast to ovarian cancer varies with the location of the BRCA1 mutation. To determine whether germline mutations in BRCA2 are associated with a similar variation in phenotypic risk, we have analysed the distribution of mutations in 25 families with multiple cases of breast and/or ovarian cancer ascertained in the United Kingdom and Eire. These mutations all lead to premature truncation of BRCA2 as a result of frameshift deletions/insertions or nonsense mutations. Analysis of the mutation distribution along the length of the gene indicates a significant genotype-phenotype correlation. Truncating mutations in families with the highest risk of ovarian cancer relative to breast cancer are clustered in a region of approximately 3.3 kb in exon 11 (P = 0.0004). Published data on mutations in 45 other BRCA2-linked families provide support for this correlation.
 ...
PMID:Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. 898 79

Two cancer susceptibility genes, BRCA1 on chromosome 17q12-21 and BRCA2 on chromosome 13q12-13, are thought to be responsible for approximately 80% of families containing multiple cases of early-onset female breast cancer. Germline mutations of BRCA1 are also associated with ovarian cancer and mutations of BRCA2 are associated with an increased risk of male breast cancer, ovarian cancer, prostate cancer and pancreatic cancer. The recent isolation of both genes should make possible the identification of the genetic defect that predisposes affected individuals to breast and ovarian cancer and might lead to the use of genetic information for predictive testing.
 ...
PMID:Mutations of the BRCA1 and BRCA2 genes and the possibilities for predictive testing. 913 30


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