High resolution analysis of DNA copy-number aberrations of chromosomes 8, 13, and 20 in gastric cancers

DNA copy-number gains of chromosomes 8q, 13q, and 20q are frequently observed in gastric cancers. Moreover gain of chromosome 20q has been associated with lymph node metastasis. The aim of this study was to correlate DNA copy-number changes of individual genes on chromosomes 8q, 13q, and 20q in gastric adenocarcinomas to clinicopathological data. DNA isolated from 63 formalin-fixed and paraffin-embedded gastric adenocarcinoma tissue samples was analyzed by whole-genome microarray comparative genomic hybridization and by multiplex ligation-dependent probe amplification (MLPA), targeting 58 individual genes on chromosomes 8, 13, and 20. Using array comparative genomic hybridization, gains on 8q, 13q, and 20q were observed in 49 (77.8%), 25 (39.7%), and 49 (77.8%) gastric adenocarcinomas, respectively. Gain of chromosome 20q was significantly correlated with lymph node metastases (p = 0.05) and histological type (p = 0.02). MLPA revealed several genes to be frequently gained in DNA copy number. The oncogene c-myc on 8q was gained in 73% of the cancers, while FOXO1A and ATP7B on 13q were both gained in 28.6% of the cases. Multiple genes on chromosome 20q showed gains in more than 60% of the cancers. DNA copy-number gains of TNFRSF6B (20q13.3) and ZNF217 (20q13.2) were significantly associated with lymph node metastasis (p = 0.02) and histological type (p = 0.02), respectively. In summary, gains of chromosomes 8q, 13q, and 20q in gastric adenocarcinomas harbor DNA copy-number gains of known and putative oncogenes. ZNF217 and TNFRSF6B are associated with important clinicopathological variables, including lymph node status

Quality Assurance When Developing Software with a Medical Purpose

In the field of development of scientific or medical software, questions may arise, such as how we define if software has a “medical purpose,” what regulations may apply and how they influence the (projected) pathway. We may find ourselves embroiled with the new “In Vitro Diagnostics Regulation” (IVDR) and its implementation in organizations. In this chapter we will attempt to summarize and order key bits of information, as found in these standards and related publications, that seemed relevant along the way in our software development processes. After this we will try to expose possible pitfalls that could be encountered. We also reach out to (existing) methodologies that may aid in the endeavor to the realization of software. Top-down risk approaches consider hierarchical ordering of priorities based on process levels where context and meaning play a more significant role over content and documentation. To honor the different sources, we will seek to outline how this led to a form of understanding that allowed the development of software. Maintaining a high standard of risk control while keeping focus on product realization. Hopefully these outlines and referred source materials may bring slight relief to others on a similar quest

MLPAnalyzer: Data Analysis Tool for Reliable Automated Normalization of MLPA Fragment Data

Background: Multiplex Ligation dependent Probe Amplification (MLPA) is a rapid, simple, reliable and customized method for detection of copy number changes of individual genes at a high resolution and allows for high throughput analysis. This technique is typically applied for studying specific genes in large sample series. The large amount of data, dissimilarities in PCR efficiency among the different probe amplification products, and sample-to-sample variation pose a challenge to data analysis and interpretation. We therefore set out to develop an MLPA data analysis strategy and tool that is simple to use, while still taking into account the above-mentioned sources of variation

Correction: BRCA1 and BRCA2 mutational profile and prevalence in hereditary breast and ovarian cancer (HBOC) probands from Southern Brazil: Are international testing criteria appropriate for this specific population?

[This corrects the article DOI: 10.1371/journal.pone.0187630.]

BRCA1 and BRCA2 mutational profile and prevalence in hereditary breast and ovarian cancer (HBOC) probands from Southern Brazil : are international testing criteria appropriate for this specific population?

Background Germline pathogenic variants in BRCA1 and BRCA2 (BRCA) are the main cause of Hereditary Breast and Ovarian Cancer syndrome (HBOC). Methods In this study we evaluated the mutational profile and prevalence of BRCA pathogenic/likely pathogenic variants among probands fulfilling the NCCN HBOC testing criteria. We characterized the clinical profile of these individuals and explored the performance of international testing criteria. Results A pathogenic/likely pathogenic variant was detected in 19.1% of 418 probands, including seven novel frameshift variants. Variants of uncertain significance were found in 5.7% of individuals. We evaluated 50 testing criteria and mutation probability algorithms. There was a significant odds-ratio (OR) for mutation prediction (p 0.05) for 25 criteria; 14 of these had p 0.001. Using a cutoff point of four criteria, the sensitivity is 83.8%, and the specificity is 53.5% for being a carrier. The prevalence of pathogenic/likely pathogenic variants for each criterion ranged from 22.1% to 55.6%, and criteria with the highest ORs were those related to triple-negative breast cancer or ovarian cancer. Conclusions This is the largest study of comprehensive BRCA testing among Brazilians to date, and the first to analyze clinical criteria for genetic testing. Several criteria that are not included in the NCCN achieved a higher predictive value. Identification of the most informative criteria for each population will assist in the development of a rational approach to genetic testing, and will enable the prioritization of high-risk individuals as a first step towards offering testing in low-income countries

L'Auto-vélo : automobilisme, cyclisme, athlétisme, yachting, aérostation, escrime, hippisme / dir. Henri Desgranges

26 octobre 19301930/10/26 (A31,N10907)

Classification of the variants of uncertain significance (VUS) found in our cohort according to different databases and their effects as predicted by <i>in silico</i> models.

<p>Classification of the variants of uncertain significance (VUS) found in our cohort according to different databases and their effects as predicted by <i>in silico</i> models.</p

Performance of three distinct criteria sets.

<p>Considering all criteria (N = 54, dashed blue line); considering only criteria with p ≤ 0.05 in the OR analysis (N = 25, dashed green line); and considering only criteria with p ≤ 0.001 in the same analysis (N = 14, solid purple line).</p