269 research outputs found
Letter to the editor RE: The association between high oral intake of acrylamide and risk of breast cancer: An updated systematic review and meta-analysis
No full textHogervorst, J (corresponding author), Hasselt Univ, Ctr Environm Sci, B-3590 Diepenbeek, Belgium.
[email protected]
Tumor characteristics as an analytic tool for classifying genetic variants of uncertain clinical significance
No full textIt is important to identify a germline mutation in a patient with an inherited cancer syndrome to allow mutation carriers to be included in cancer surveillance programs, which have been proven to save lives. Many of the mutations identified result in premature termination of translation, and thus in loss-of-function of the encoded mutated protein. However, the significance of a large proportion of the sequence changes reported is unknown. Some of these variants will be associated with a high risk of cancer and have direct clinical consequence. Many criteria can be used to classify variants with unknown significance; most criteria are based on the characteristics of the amino acid change, on segregation data and appearance of the variant, on the presence of the variant in controls, or on functional assays. In inherited cancers, tumor characteristics can also be used to classify variants. It is worthwhile to examine the clinical, morphological and molecular features of a patient, and his or her family, when assessing whether the role of a variant is likely to be neutral or pathogenic. Here we describe the advantages and disadvantages of using the tumor characteristics of patients carrying germline variants of uncertain significance (VUS) in BRCA1, BRCA2, or in one of the mismatch repair (MMR) genes, MLH1, MSH2, or MSH6, to infer pathogenicity. Hum Mutat 29(11), 1292–1303, 200
Longitudinal evidence of the impact of normal thyroid stimulating hormone variations on cognitive functioning in very old age
No full textThe purpose of this study was to examine longitudinal associations among thyroid stimulating hormone (TSH) levels and cognitive performance. Data collected at the first three assessment times, approximately 3 years apart, are reported for the survivors (n=45) from a previously published cross-sectional study. Participants were aged 75–93 years at baseline, and data reported were collected in the Kungsholmen Project, a longitudinal project investigating aging and dementia. Analyses revealed that although declining verbal fluency and visuospatial abilities were accompanied by simultaneously declining TSH levels, the pattern of cross-sectional and longitudinal results are interpreted such that declining TSH levels may have caused episodic memory deficits later on. These results were obtained in the examination of 6-year but not 3-year change, and after removal of the cognitive variation associated with depressive mood symptoms
Clinical testing of BRCA1 and BRCA2: A worldwide snapshot of technological practices
No full textClinical testing of BRCA1 and BRCA2 began over 20 years ago. With the expiration and overturning of the BRCA patents, limitations on which laboratories could offer commercial testing were lifted. These legal changes occurred approximately the same time as the widespread adoption of massively parallel sequencing (MPS) technologies. Little is known about how these changes impacted laboratory practices for detecting genetic alterations in hereditary breast and ovarian cancer genes. Therefore, we sought to examine current laboratory genetic testing practices for BRCA1/BRCA2. We employed an online survey of 65 questions covering four areas: laboratory characteristics, details on technological methods, variant classification, and client-support information. Eight United States (US) laboratories and 78 non-US laboratories completed the survey. Most laboratories (93%; 80/86) used MPS platforms to identify variants. Laboratories differed widely on: (1) technologies used for large rearrangement detection; (2) criteria for minimum read depths; (3) non-coding regions sequenced; (4) variant classification criteria and approaches; (5) testing volume ranging from 2 to 2.5 × 105 tests annually; and (6) deposition of variants into public databases. These data may be useful for national and international agencies to set recommendations for quality standards for BRCA1/BRCA2 clinical testing. These standards could also be applied to testing of other disease genes.</p
The Protein Truncation Test (PTT) for Rapid Detection of Translation-Terminating Mutations
No full textA CENTURY AFTER LYMAN
No full textT. Lyman, Astroph. J. E. Reinhold, W. Hogervorst, and W. Ubachs, Phys. Rev. Lett. A. de Lange E. Reinhold, and W. Ubachs, Phys. Rev. Lett. A. de Lange, E. Reinhold, and W. Ubachs, Int. Rev. Phys. Chem. E. Reinhold and W. Ubachs, Phys. Rev. Lett. W. Ubachs and E. Reinhold, Phys. Rev. Lett. accepted (2004).Author Institution: Laser Centre, Department of Physics and Astronomy, Vrije UniversiteitExactly a century ago Lyman reported on the first spectroscopic identification of the hydrogen . Over the years past many spectroscopists have searched for spectral signatures of the smallest neutral molecule, which has become the fundamental test system for quantum chemical ab initio calculations. Experimental work on and its isotopomers is more difficult than in other systems because electronic absorption occurs only at wavelengths ; the vibrational spectrum is extremely weak due to the inversion symmetry; due to the low nuclear mass spectra are not organized in bands as bands but rather occur as randomly organized lines; isotopic substitution is not helpful because it gives rise to another set of randomly appearing lines. In the past decade we have employed laser based techniques to unravel new spectral structures in hydrogen and measure at high resolution. Specific breakthroughs are the use of a narrowband tunable laser in the extreme ultraviolet domain and of multiple-resonance techniques involving XUV photons. These studies have led to: the observation of high-lying double-well structures of gerade ; the observation of a double-well structures of ungerade ; the observation of strong u-g symmetry ; the observation of heavy Rydberg states of the . From a comparison of extremely accurate calibration of Lyman and Werner transitions, and by comparing the laboratory results with absorptions in spectra of quasars that have occured 12 Billion years ago, a rather strict constraint can be set om a possible variation of the proton-to-electron mass
Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers.
No full textSeveral common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2)
Prediction of BRCA2-association in hereditary breast carcinomas using array-CGH
No full textGermline mutations in BRCA1/2 increase the lifetime risk for breast and ovarian cancer dramatically. Identification of such mutations is important for optimal treatment decisions and pre-symptomatic mutation screening in family members. Although current DNA diagnostics is able to identify many different mutations, it remains unclear, how many BRCA2-associated breast cancer cases remain unidentified as such. In addition, mutation scanning detects many unclassified variants (UV) for which the clinical relevance is uncertain. Therefore, our aim was to develop a test to identify BRCA2-association in breast tumors based on the genomic signature. A BRCA2-classifier was built using array-CGH profiles of 28 BRCA2-mutated and 28 sporadic breast tumors. The classifier was validated on an independent group of 19 BRCA2-mutated and 19 sporadic breast tumors. Subsequently, we tested 89 breast tumors from suspected hereditary breast (and ovarian) cancer (HBOC) families, in which either no BRCA1/2 mutation or an UV had been found by routine diagnostics. The classifier showed a sensitivity of 89% and specificity of 84% on the validation set of known BRCA2-mutation carriers and sporadic tumor cases. Of the 89 HBOC cases, 17 presented a BRCA2-like profile. In three of these cases additional indications for BRCA2-deficiency were found. Chromosomal aberrations that were specific for BRCA2-mutated tumors included loss on chromosome arm 13q and 14q, and gain on 17q. Since we could separate BRCA1-like, BRCA2-like, and sporadic-like tumors, using our current BRCA2- and previous BRCA1-classifier, this method of breast tumor classification could be applied as additional test for current diagnostics to help clinicians in decision making and classifying sequence variants of unknown significance.Tumourgenetics and immunogenetic
Expression of the Human Dp 71 (Apo-Dystrophin-1 ) Gene from a 760-kb DMD-YAC Transferred to Mouse Cells
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