Methylation of MGMT and ADAMTS14 in normal colon mucosa : biomarkers of a field defect for cancerization preferentially targeting elder African-Americans

Altres ajuts: National Institutes of Health Grant R37CA63585, RO1CA83017 i RO1CA157328Somatic hypermethylation of the O6-methylguanine-DNA methyltransferase gene (MGMT) was previously associated with G > A transition mutations in KRAS and TP53 in colorectal cancer (CRC). We tested the association of MGMT methylation with G > A mutations in KRAS and TP53 in 261 CRCs. Sixteen cases, with and without MGMT hypermethylation, were further analyzed by exome sequencing. No significant association of MGMT methylation with G > A mutations in KRAS, TP53 or in the whole exome was found (p > 0.5 in all comparisons). The result was validated by in silico comparison with 302 CRCs from The Cancer Genome Atlas (TCGA) consortium dataset. Transcriptional silencing associated with hypermethylation and stratified into monoallelic and biallelic. We also found a significant clustering (p = 0.001) of aberrant hypermethylation of MGMT and the matrix metalloproteinase gene ADAMTS14 in normal colonic mucosa of CRC patients. This suggested the existence of an epigenetic field defect for cancerization disrupting the methylation patterns of several loci, including MGMT or ADAMTS14, that may lead to predictive biomarkers for CRC. Methylation of these loci in normal mucosa was more frequent in elder (p = 0.001) patients, and particularly in African Americans (p = 1 × 10-5), thus providing a possible mechanistic link between somatic epigenetic alterations and CRC racial disparities in North Americ

Proteomics of endometrial cancer diagnosis, treatment, and prognosis

This review discusses the current status of proteomics technology in endometrial cancer diagnosis, treatment and prognosis. The first part of this review focuses on recently identified biomarkers for endometrial cancer, their importance in clinical use as well as the proteomic methods used in their discovery. The second part highlights some of the emerging mass spectrometry based proteomic technologies that promise to contribute to a better understanding of endometrial cancer by comparing the abundance of hundreds or thousands of proteins simultaneously.Parul Mittal, Manuela Klingler-Hoffmann, Georgia Arentz, Chao Zhang, Gurjeet Kaur, Martin K. Oehler, and Peter Hoffman

Validation of mutated <i>CEBPA</i> bZIP as a distinct prognosis entity in acute myeloid leukemia: a study by the Spanish PETHEMA registry

Not available

Molecular Studies for the Early Detection of Philadelphia-Negative Myeloproliferative Neoplasms

JAK2 V617F is the predominant driver mutation in patients with Philadelphia-negative myeloproliferative neoplasms (MPN). JAK2 mutations are also frequent in clonal hematopoiesis of indeterminate potential (CHIP) in otherwise “healthy” individuals. However, the period between mutation acquisition and MPN diagnosis (known as latency) varies widely between individuals, with JAK2 mutations detectable several decades before diagnosis and even from birth in some individuals. Here, we will review the current evidence on the biological factors, such as additional mutations and chronic inflammation, which influence clonal expansion and may determine why some JAK2-mutated individuals will progress to an overt neoplasm during their lifetime while others will not. We will also introduce several germline variants that predispose individuals to CHIP (as well as MPN) identified from genome-wide association studies. Finally, we will explore possible mutation screening or interventions that could help to minimize MPN-associated cardiovascular complications or even delay malignant progression

ORFISH - Development of innovative, low-impact offshore fishing practices for small-scale vessels in outermost regions - MARE/2015/06. WP2 Raising awareness of the opportunities to develop innovative fishing techniques

The database presented in this report is an exhaustive review of existing technical information on experimental fishing. This review has been done over a period covering the last 30 years based on available literature, databases and reports. For each outermost region (OR), several universities and public investigation centres have also been consulted.     All the non-published reports and papers presented in this database will be gradually scanned and published on the ORFISH website in order to make them publi

ORFISH - Development of innovative, low-impact offshore fishing practices for small-scale vessels in outermost regions - MARE/2015/06. WP4. Creating alternative sustainable fishing opportunities

One of the key goals of this report is to compare the fisheries governance systems in the different outermost regions in the context of the Common Fishery Policy (CFP). By fisheries governance systems, we mean the different institutions and the collective action processes by which decision making in fisheries management is established and the different set of laws, rules set for the regulation of the fishing activities. The Common Fishery Policy is often seen as a top-down process and the aim of the task was to identify and compare the role of fisher organizations and regional administration in the management of fisheries resources. Based on a better understanding of how each organization is functioning and which type of competencies such organizations have concerning resources management, a comparison could also strengthen the links between the different fishers organizations in the perspective of the new advisory council for the ORs but not only. Another objective is also to identify good practices (but also drawbacks of current regulations) with particular emphasis on whether or not these models could be used as examples in other ORs, in order to ensure long-term sustainable fisheries contributing to the CFP objectives. That is why, a complementary objective was to provide a detailed analysis of the regulations which apply in each ORs to identify the origin (EU, national, regional, local) of the different measures, their objectives (fisheries regulation, ecosystem and biodiversity conservation, …) and the characteristics of the regulations in terms of scope (conservation measures, access regulation measures including conflict regulation between fishing activities)

Molecular landscape and validation of new genomic classification in 2668 adult AML patients: real life data from the PETHEMA registry

Next–Generation Sequencing (NGS) implementation to perform accurate diagnosis in acute myeloid leukemia (AML) represents a major challenge for molecular laboratories in terms of specialization, standardization, costs and logistical support. In this context, the PETHEMA cooperative group has established the first nationwide diagnostic network of seven reference laboratories to provide standardized NGS studies for AML patients. Cross–validation (CV) rounds are regularly performed to ensure the quality of NGS studies and to keep updated clinically relevant genes recommended for NGS study. The molecular characterization of 2856 samples (1631 derived from the NGS–AML project; NCT03311815) with standardized NGS of consensus genes (ABL1, ASXL1, BRAF, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, GATA2, HRAS, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NPM1, NRAS, PTPN11, RUNX1, SETBP1, SF3B1, SRSF2, TET2, TP53, U2AF1 and WT1) showed 97% of patients having at least one mutation. The mutational profile was highly variable according to moment of disease, age and sex, and several co–occurring and exclusion relations were detected. Molecular testing based on NGS allowed accurate diagnosis and reliable prognosis stratification of 954 AML patients according to new genomic classification proposed by Tazi et al. Novel molecular subgroups, such as mutated WT1 and mutations in at least two myelodysplasia–related genes, have been associated with an adverse prognosis in our cohort. In this way, the PETHEMA cooperative group efficiently provides an extensive molecular characterization for AML diagnosis and risk stratification, ensuring technical quality and equity in access to NGS studies

Methylation of MGMT and ADAMTS14 in normal colon mucosa : biomarkers of a field defect for cancerization preferentially targeting elder African-Americans

Altres ajuts: National Institutes of Health Grant R37CA63585, RO1CA83017 i RO1CA157328Somatic hypermethylation of the O6-methylguanine-DNA methyltransferase gene (MGMT) was previously associated with G > A transition mutations in KRAS and TP53 in colorectal cancer (CRC). We tested the association of MGMT methylation with G > A mutations in KRAS and TP53 in 261 CRCs. Sixteen cases, with and without MGMT hypermethylation, were further analyzed by exome sequencing. No significant association of MGMT methylation with G > A mutations in KRAS, TP53 or in the whole exome was found (p > 0.5 in all comparisons). The result was validated by in silico comparison with 302 CRCs from The Cancer Genome Atlas (TCGA) consortium dataset. Transcriptional silencing associated with hypermethylation and stratified into monoallelic and biallelic. We also found a significant clustering (p = 0.001) of aberrant hypermethylation of MGMT and the matrix metalloproteinase gene ADAMTS14 in normal colonic mucosa of CRC patients. This suggested the existence of an epigenetic field defect for cancerization disrupting the methylation patterns of several loci, including MGMT or ADAMTS14, that may lead to predictive biomarkers for CRC. Methylation of these loci in normal mucosa was more frequent in elder (p = 0.001) patients, and particularly in African Americans (p = 1 × 10-5), thus providing a possible mechanistic link between somatic epigenetic alterations and CRC racial disparities in North Americ