• MeSH
• biochemie MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biochemie
• NLK Publikační typ
• kolektivní monografie

• Publikační typ
• abstrakt z konference MeSH

• MeSH
• biochemie MeSH
• chemie MeSH
• klinická chemie MeSH
• lékařství MeSH

• Konspekt
• Lékařské vědy. Lékařství
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• chemie, klinická chemie
• biochemie
• lékařství
• NLK Publikační typ
• učebnice vysokých škol

Carcinoembryonic antigen (CEA) is widely used as a serum tumor marker in various types of cancer. Several systems for the CEA-RT-PCR approach have been reported to date. In this study, we have evaluated the quantitative CEA-RT-PCR as a diagnostic tool for detection of isolated tumor cells in bone marrow of early breast cancer patients prior to the administration of any adjuvant systemic therapy. We obtained bone marrow aspirates of 70 patients with stage I (37%), II (60%), and III (3%) breast cancer who underwent either immediate complete resection of the tumor or neoadjuvant therapy with subsequent curative surgery. mRNA was isolated using QIAamp RNA blood mini kit (Qiagen). Subsequently quantitative RT-PCR for the expression of CEA has been performed. CEA transcripts were detected in samples from 29 (41%) out of 70 patients. With a median follow-up of 22 months we observed 8 disease free survival (DFS) events including 4 systemic recurrences, 1 ductal in-situ carcinoma (DCIS), 1 local recurrence, and 2 deaths without tumour. Four DFS events (2 systemic recurrences, 2 deaths without tumor) occurred in patients with CEA transcripts in the bone marrow and 4 (2 systemic recurrences, 1 DCIS, 1 locoregional recurrence) in patients without CEA in the bone marrow. There was a trend to shorter DFS in the group with CEA in the bone marrow (p=0.05548). Overall survival was not assessed because only 2 deaths (both in patients without tumor) have been reported to date. Quantitative RT-PCR assay for CEA may be a useful tool for detection of occult breast cancer cells in the bone marrow. Clinical and prognostic relevance of minimal residual disease using this technique remains unproven. Our results should be interpreted with caution with regard to 2 deaths in CEA positive group with no relationship to disease recurrence.

• MeSH
• dospělí MeSH
• financování organizované MeSH
• Kaplanův-Meierův odhad MeSH
• karcinoembryonální antigen analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery MeSH
• nádory kostní dřeně diagnóza   sekundární   MeSH
• nádory prsu patologie   terapie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí metody   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• hodnotící studie MeSH

• MeSH
• biochemie MeSH
• Publikační typ
• biografie MeSH

• O autorovi
• Duchoň, Jiří, 1927-2009 Autorita

• MeSH
• chemie MeSH
• přijímací zkouška na vysokou školu MeSH
• studium lékařství MeSH

• Konspekt
• Chemie. Mineralogické vědy
• NLK Obory
• chemie, klinická chemie
• NLK Publikační typ
• testy

• MeSH
• finanční podpora výzkumu jako téma MeSH
• karcinoembryonální antigen diagnostické užití   MeSH
• lidé MeSH
• metastázy nádorů diagnóza   MeSH
• nádorové cirkulující buňky MeSH
• nádory kostní dřeně diagnóza   MeSH
• nádory prsu diagnóza   komplikace   MeSH
• polymerázová řetězová reakce s reverzní transkripcí metody   využití   MeSH
• prospektivní studie MeSH
• reziduální nádor diagnóza   MeSH
• vyšetřování kostní dřeně metody   využití   MeSH
• Check Tag
• lidé MeSH

Germline mutations in two major susceptibility genes BRCA1 and BRCA2 contribute to the majority of inherited breast and ovarian cancers. Besides the germline mutation, tumor progression depends on the loss of a wild-type allele. Allelic losses in the BRCA1 and BRCA2 loci have also been detected in a high proportion of sporadic breast tumors, suggesting the role of these genes in the development of non-inherited breast cancer. Forty unselected breast tumors were analyzed for the loss of heterozygosity (LOH) at BRCA1 and BRCA2 regions and tumors with allelic deletions were screened for the presence of acquired genetic alterations in respective genes. 21.1% of 38 informative tumor samples carried LOH at the BRCA1 locus whereas 33.3% of 39 informative samples showed LOH at the BRCA2 locus. Pathogenic truncating mutations in the BRCA1 gene were found in two tumor samples with allelic losses, whereas no mutations were identified in the BRCA2 gene. Mutations were not detected in non-tumor samples from the same individuals, which indicated that the BRCA1 allele was inactivated by somatic mutations in tumor tissue. The c.1116G>A (1235G>A) nonsense mutation (p.W372X) belongs to the genetic abnormalities detected infrequently in hereditary tumors; the c.3862delG (3981delG) frameshift mutation (p.E1288fsX1306) is a novel gene alteration. The occurrence of inactivating somatic mutations in sporadic breast tumors suggested the role of the BRCA1 gene in tumorigenesis in at least a minor group of patients with non-familial breast cancer. (c) 2005 Wiley-Liss, Inc.

• MeSH
• DNA nádorová genetika   MeSH
• dospělí MeSH
• duktální karcinom prsu genetika   MeSH
• geny BRCA1 * MeSH
• geny BRCA2 MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrosatelitní repetice MeSH
• mutační analýza DNA MeSH
• nádorová transformace buněk genetika   MeSH
• nádory prsu * genetika   MeSH
• nesmyslný kodon MeSH
• posun čtecího rámce na ribozómech * MeSH
• protein BRCA1 MeSH
• ztráta heterozygozity MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH

BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes have been shown to account for the majority of hereditary breast and ovarian cancers. The purpose of our study was to estimate the incidence and spectrum of pathogenic mutations in BRCA1/2 genes in high-risk Czech families. METHODS: A total of 96 Czech families with recurrent breast and/or ovarian cancer and 55 patients considered to be at high-risk but with no reported family history of cancer were screened for mutations in the BRCA1/2 genes. The entire coding sequence of each gene was analyzed using a combination of the protein truncation test and direct DNA sequencing. RESULTS: A total of 35 mutations in the BRCA1/2 genes were identified in high-risk families (36.5%). Pathogenic mutations were found in 23.3% of breast cancer families and in 59.4% of families with the occurrence of both breast and ovarian cancer. In addition, four mutations were detected in 31 (12.9%) women with early onset breast cancer. One mutation was detected in seven (14.3%) patients affected with both a primary breast and ovarian cancer and another in three (33.3%) patients with a bilateral breast cancer. A total of 3 mutations in BRCA1 were identified among 14 (21.4%) women with a medullary breast carcinoma. Of 151 analyzed individuals, 35 (23.2%) carried a BRCA1 mutation and 9 (6.0%) a BRCA2 mutation. One novel truncating mutation was found in BRCA1 (c.1747A>T) and two in BRCA2 (c.3939delC and c.5763dupT). The 35 identified BRCA1 mutations comprised 13 different alterations. Three recurrent mutations accounted for 71.4% of unrelated individuals with detected gene alterations. The BRCA1 c.5266dupC (5382insC) was detected in 51.4% of mutation positive women. The mutations c.3700_3704del5 and c.181T>G (300T>G) contributed to 11.4% and 8.6% of pathogenic mutations, respectively. A total of eight different mutations were identified in BRCA2. The novel c.5763dupT mutation, which appeared in two unrelated families, was the only recurrent alteration of the BRCA2 gene identified in this study. CONCLUSION: Mutational analysis of BRCA1/2 genes in 151 high-risk patients characterized the spectrum of gene alterations and demonstrated the dominant role of the BRCA1 c.5266dupC allele in hereditary breast and ovarian cancer.

• MeSH
• amplifikace genu MeSH
• DNA nádorová genetika   krev   MeSH
• etnicita genetika   MeSH
• exony MeSH
• financování organizované MeSH
• geny BRCA1 MeSH
• geny BRCA2 MeSH
• lidé MeSH
• mutační analýza DNA MeSH
• nádory prsu genetika   MeSH
• nádory vaječníků genetika   MeSH
• polymerázová řetězová reakce MeSH
• rizikové faktory MeSH
• RNA nádorová genetika   krev   MeSH
• rodina MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

• MeSH
• dospělí MeSH
• finanční podpora výzkumu jako téma MeSH
• geny BRCA1 MeSH
• geny BRCA2 MeSH
• lidé MeSH
• mutace genetika   MeSH
• nádory prsu diagnóza   epidemiologie   genetika   MeSH
• proteinkinasy genetika   MeSH
• sekvenční analýza DNA MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Česká republika MeSH