120 research outputs found
Determination of the frequency of the common 657Del5 Nijmegen breakage syndrome mutation in the German population: no association with risk of breast cancer
No full textNijmegen breakage syndrome (NBS) is an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. It shares a number of features with the Ataxia telangiectasia (AT) syndrome: the most notable are high sensitivity to ionizing radiation and predisposition to cancer. Recently, the gene responsible for NBS has been identified on chromosome band 8q21. It encodes a DNA double-strand break repair protein, named Nibrin. A truncating 5-bp deletion (657Del5) has been identified in 90% of NBS patients and this is presumed to be of Slavic origin. There is evidence that heterozygous AT mutation carriers are predisposed to breast cancer. Since the NBS phenotype at the cellular level is very similar to AT, we have screened 477 German breast cancer patients, aged under 51 years, and 866 matched controls for the common NBS mutation. We have identified one carrier among the cases and one among the controls, indicating that the population frequency of this NBS mutation is 1 in 866 people (95% CI = 1 in 34,376 to 1 in 156) and the estimated prevalence of NBS is thus 1 in 3 million people. The proportion of breast cancer attributable to this mutation is less than 1%
Comparison of DNA repair protein expression and activities between human fibroblast cell lines with different radiosensitivities
No full textIn order to investigate the molecular basis of variation in response to ionising radiation (IR) in radiotherapy patients, we have studied the expression of several genes involved in DNA double-strand break repair pathways in fibroblast cell lines. Ten lines were established from skin biopsies of cancer patients with different normal-tissue reactions to IR, and 3 from a control individual. For all 10 test cell lines, the cellular radiosensitivity was also known. Using Western blots we measured, in non-irradiated cells, the basal expression levels of ATM, Rad1 and Hus1, involved in the control of cellular DNA damage checkpoints, together with DNA-PKcs, Ku70, Ku80; XRCC4, ligaseIV and Rad51, involved in radiation- induced DSB repair. We also analysed the in vitro enzymatic activities, under non-irradiated conditions, of the DNA-PK and XRCC4/ligaseIV complexes. The levels of expression of the different proteins were similar in all the cell lines, but the activities of the DNA-PK and XRCC4/ligaseIV complexes showed some differences. These differences did not correlate with either the normal tissue response of the patient in vivo or with cellular radiation sensitivity in vitro. The activity differences of these enzyme complexes, therefore, do not account for the variation of responses seen between patients
BRCA1 and BRCA2 mutations in a population-based study of male breast cancer
No full textBackground: The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC)
in the United Kingdom is not known, and the importance of these genes in the increased risk of female
breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear.
Methods: We have carried out a population-based study of 94 MBC cases collected in the UK. We
screened genomic DNA for mutations in BRCA1 and BRCA2 and used family history data from these
cases to calculate the risk of breast cancer to female relatives of MBC cases. We also estimated the
contribution of BRCA1 and BRCA2 to this risk.
Results: Nineteen cases (20%) reported a first-degree relative with breast cancer, of whom seven also
had an affected second-degree relative. The breast cancer risk in female first-degree relatives was 2.4
times (95% confidence interval [CI] = 1.4–4.0) the risk in the general population. No BRCA1 mutation
carriers were identified and five cases were found to carry a mutation in BRCA2. Allowing for a
mutation detection sensitivity frequency of 70%, the carrier frequency for BRCA2 mutations was 8%
(95% CI = 3–19). All the mutation carriers had a family history of breast, ovarian, prostate or
pancreatic cancer. However, BRCA2 accounted for only 15% of the excess familial risk of breast
cancer in female first-degree relatives.
Conclusion: These data suggest that other genes that confer an increased risk for both female and
male breast cancer have yet to be found
A comprehensive model for familial breast cancer incorporating BRCA1, BRCA2 and other genes.
No full textIn computing the probability that a woman is a BRCA1 or BRCA2 carrier for genetic counselling purposes, it is important to allow for the fact that other breast cancer susceptibility genes may exist. We used data from both a population based series of breast cancer cases and high risk families in the UK, with information on BRCA1 and BRCA2 mutation status, to investigate the genetic models that can best explain familial breast cancer outside BRCA1 and BRCA2 families. We also evaluated the evidence for risk modifiers in BRCA1 and BRCA2 carriers. We estimated the simultaneous effects of BRCA1, BRCA2, a third hypothetical gene 'BRCA3', and a polygenic effect using segregation analysis. The hypergeometric polygenic model was used to approximate polygenic inheritance and the effect of risk modifiers. BRCA1 and BRCA2 could not explain all the observed familial clustering. The best fitting model for the residual familial breast cancer was the polygenic, although a model with a single recessive allele produced a similar fit. There was also significant evidence for a modifying effect of other genes on the risks of breast cancer in BRCA1 and BRCA2 mutation carriers. Under this model, the frequency of BRCA1 was estimated to be 0.051% (95% CI: 0.021-0.125%) and of BRCA2 0.068% (95% CI: 0.033-0.141%). The breast cancer risk by age 70 years, based on the average incidence over all modifiers was estimated to be 35.3% for BRCA1 and 50.3% for BRCA2. The corresponding ovarian cancer risks were 25.9% for BRCA1 and 9.1% for BRCA2. The findings suggest that several common, low penetrance genes with multiplicative effects on risk may account for the residual non-BRCA1/2 familial aggregation of breast cancer. The modifying effect may explain the previously reported differences between population based estimates for BRCA1/2 penetrance and estimates based on high-risk families
"Da Patchen a Baj: paesaggi e poesaggi"
No full textIl saggio analizza la metamorfosi del neologismo "poemscapes" (poesaggi) e del genere letterario, la metamorfosi compiutasi nella traduzione italiana a cura di Lina Angioletti e, infine, quella del codice linguistico in codice iconografico grazie alle illustrazioni di Enrico Baj nell’edizione italiana. L’autrice valuta, inoltre, la portata dei “Poemscapes”nel quadro dell'opera dell'artista figurativo che, nell’edizione di Guanda a cura di Roberto Sanesi, ne allarga l'orizzonte visivo. Il risultato estetico dell’operazione conduce alla riterritorializzazione dei significati che rispondono a una dinamica struttura a rizoma in continua trasformazione. Gli strumenti metodologici utilizzati s'inseriscono nel quadro dell'analisi testuale, dell'appoccio fenomenologico all'estetica, degli studi culturali.In "From Patchen to Baj: landscapes and poemscapes" the author analyzes the metamorphosis of the neologism “poemscapes” (the title of a Kenneth Patchen’s collection of prose poems) into a word connoting a literary genre. She then examines Lina Angioletti’s translation (or metamorphosis) into Italian and, finally, the way in which elements from the poem's linguistic code are turned, in Enrico Baj’s drawings that illustrate the Italian edition, into iconographic matter. The effect of the visual apparatus in the Guanda edition (by Roberto Sanesi) is that of widening the reader-observer’s horizon. The final aesthetic result of the operation leads to a reterritorialization of meanings making up a rhizomatic structure in an everlasting metamorphosis. The methodological instruments used range from textual analysis to the phenomenological approach to aesthetics, to cultural studies
Triple decomposition of a fluctuating velocity field in a multiscale flow
No full textA method for the triple decomposition of fluctuating velocity in a multiscale flow, suitable for a spatiotemporal data set, is presented. It is applied to experimental data gathered by means of particle image velocimetry (PIV). The basic properties of the decomposed parts are shown. The presented method is then used to perform a conditional study on the residual transverse velocity fluctuations. It was found that phase locking occurs between the stochastic fluctuations embedded in the wakes of different bars, appearing after the wakes have merged
Refined localization to contiguous regions on chromosome 10q of the two genes (H4 and RET) that form the oncogenic sequence PTC
No full textIn this report we confirm the localization of the human RET proto-oncogene to chromosome 10q11.2, both by Southern blot analysis of a panel of human-rodent somatic cell hybrids and by in situ hybridization on human metaphase chromosomes. Previously, we had assigned to the same chromosome region the gene termed H4. In about 25% of papillary thyroid carcinomas, this gene was shown to rearrange with RET to give rise to the transforming sequence PTC. The analysis of different cell hybrids containing subfragments of chromosome 10, in conjunction with pulse field gel electrophoresis, established that H4 is mapped distally to RET at a distance not less than 280 kb. These findings suggest that intrachromosomal rearrangements are responsible for PTC activation in papillary thyroid carcinomas
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