Efficiency of BRCAPRO and Myriad II mutation probability thresholds versus cancer history criteria alone for BRCA1/2 mutation detection

Considerable differences exist amongst countries in the mutation probability methods and thresholds used to select patients for BRCA1/2 genetic screening. In order to assess the added value of mutation probability methods, we have retrospectively calculated the BRCAPRO and Myriad II probabilities in 306 probands who had previously been selected for DNA-analysis according to criteria based on familial history of cancer. DNA-analysis identified 52 mutations (16.9%) and 11 unclassified variants (UVs, 3.6%). Compared to cancer history, a threshold ≥10% with BRCAPRO or with Myriad II excluded about 40% of the patients from analysis, including four with a mutation and probabilities <10% with both programs. All four probands had a BRCA2 mutation. BRCAPRO and Myriad II showed similar specificity at 10% threshold, overall BRCAPRO was more sensitive than Myriad II for the detection of mutations. Only two of the probands with an UV had probabilities >20% with BRCAPRO and Myriad II. In summary, BRCAPRO and Myriad II are more efficient than cancer history alone to exclude patients without a mutation. BRCAPRO performs better for the detection of BRCA1 mutations than of BRCA2 mutations. The Myriad II scores provided no additional information than the BRCAPRO scores alone for the detection of patients with a mutation. The use of thresholds excluded from analysis the majority of patients carrying an UV

Nonpolypoid colorectal neoplasms: a challenge in endoscopic surveillance of patients with Lynch syndrome

Background and study aims: Patients with Lynch syndrome may develop colorectal cancer (CRC), despite intensive colonoscopic surveillance. Nonpolypoid colorectal neoplasms might be a major contributor to the occurrence of these cancers. The aim of this case - control study was to compare the endoscopic appearance of colorectal neoplasms between patients with Lynch syndrome and control individuals at average risk for CRC. Patients and methods: The endoscopists at the Maastricht University Medical Center were first given training to ensure familiarity with the appearance and classification of nonpolypoid lesions. Patients with Lynch syndrome and patients at average risk for CRC who underwent elective colonoscopy at the Center were prospectively included. Nonpolypoid lesions were defined as lesions with a height of less than half the diameter, and advanced histology was defined as the presence of high grade dysplasia or early cancer. Results: A total of 59 patients with Lynch syndrome (mean age 48.7 years, 47.5% men) and 590 matched controls (mean age 50.2 years, 47.5% men) were included. In patients with Lynch syndrome, adenomas were significantly more likely to be nonpolypoid than they were in controls: 43.3% vs. 16.9% (OR 3.60, 95%CI 1.90-6.83; P <0.001). This was particularly true for proximal adenomas: 58.1% vs. 16.3% (OR 6.93, 95%CI 2.92-16.40; P <0.001). Adenomas containing advanced histology were more often nonpolypoid in patients with Lynch syndrome than in controls (4/5, 80.0% vs. 5/17, 29.4%; P = 0.19). Serrated polyps were also more often nonpolypoid in patients with Lynch syndrome than in controls: 49.2% vs. 20.4% (OR 3.57, 95%CI 1.91-6.68; P <0.001). Conclusions: In patients with Lynch syndrome, colorectal neoplasms are more likely to have a nonpolypoid shape than those from average risk patients, especially in the proximal colon. These findings suggest that proficiency in recognition and endoscopic resection of nonpolypoid colorectal lesions are needed to ensure colonoscopic prevention against CRC in this high risk population

Des fonctions propres de l'operateur d'Orr-Sommerfeld et de son adjoint dans le cas du domaine semi-infini

Extrait de : Comptes rendus de l'Academie des Sciences Paris. Problemes mathematiques de la mecanique/Mathematical problems in mechanics, Tome 313, Serie 1, p. 817-822, 1991SIGLEAvailable at INIST (FR), Document Supply Service, under shelf-number : 22419, issue : a.1991 n.226 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

MLL2 Mutation Spectrum in 45 Patients with Kabuki Syndrome

Genetics of disease, diagnosis and treatmen