Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Peer reviewe

The Two Expeditions of the Byzantine Emperor Romanos IV Diogenes in 1068 and 1069

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Screening for TSC1 and TSC2 mutations using NGS in Greek children with tuberous sclerosis syndrome

Tuberous Sclerosis Complex (TSC) is a rare neurocutaneous syndrome inherited by an autosomal dominant manner. The disorder is commonly manifested by the presence of multiple benign tumors located in numerous tissues, including the brain, heart, skin and kidneys. Seizures, autism, developmental and behavioral delay, as well as non-neurological phenotypic findings, are suggestive of TSC. The identification of one pathogenic mutation in either the TSC1 or TSC2 genes is considered to be an independent diagnostic criterion. In our study, seventeen Greek patients, 2yo on average, were analyzed for the presence of pathogenic germline mutations in the aforementioned loci by Next-Generation Sequencing. A TSC1/2 gene panel was designed for the molecular diagnosis of the disease. Patients underwent initial diagnosis based on their clinical symptoms, most frequently involving the presence of skin lesions and/or epilepsy. Only one case was familial. Sixteen different genetic alterations were identified in TSC1 and TSC2 genes in fifteen patients, giving a 88% detection rate by employing NGS technology. Overall, most pathogenic mutations (11/15) identified were located in the TSC2 gene with exon 41 being the most frequent. With respect to genotype-phenotype association, no patient TSC1 (+) developed SEGA or renal cysts. No significant differences were observed between different types of TSC2 mutations and any clinical feature. Sequencing also revealed 18 different SNPs across the TSC1 and 20 across the TSC2 genes. This is the first registry of the genetic profile of TSC patients in Greece using a custom-made gene panel as molecular diagnostic tool. © 2018 European Paediatric Neurology Societ

Screening for TSC1 and TSC2 mutations using NGS in Greek children with tuberous sclerosis syndrome

Tuberous Sclerosis Complex (TSC) is a rare neurocutaneous syndrome inherited by an autosomal dominant manner. The disorder is commonly manifested by the presence of multiple benign tumors located in numerous tissues, including the brain, heart, skin and kidneys. Seizures, autism, developmental and behavioral delay, as well as non-neurological phenotypic findings, are suggestive of TSC. The identification of one pathogenic mutation in either the TSC1 or TSC2 genes is considered to be an independent diagnostic criterion. In our study, seventeen Greek patients, 2yo on average, were analyzed for the presence of pathogenic germline mutations in the aforementioned loci by Next-Generation Sequencing. A TSC1/2 gene panel was designed for the molecular diagnosis of the disease. Patients underwent initial diagnosis based on their clinical symptoms, most frequently involving the presence of skin lesions and/or epilepsy. Only one case was familial. Sixteen different genetic alterations were identified in TSC1 and TSC2 genes in fifteen patients, giving a 88% detection rate by employing NGS technology. Overall, most pathogenic mutations (11/15) identified were located in the TSC2 gene with exon 41 being the most frequent. With respect to genotype-phenotype association, no patient TSC1 (+) developed SEGA or renal cysts. No significant differences were observed between different types of TSC2 mutations and any clinical feature. Sequencing also revealed 18 different SNPs across the TSC1 and 20 across the TSC2 genes. This is the first registry of the genetic profile of TSC patients in Greece using a custom-made gene panel as molecular diagnostic tool. © 2018 European Paediatric Neurology Societ

Histopathological evaluation of a retinoic acid eluting stent in a rabbit iliac artery model

This study aimed to evaluate the safety and efficacy of innovative retinoic acid (RA) eluting stents with bioabsorbable polymer. Sixty stents divided in ten groups were implanted in the iliac arteries of 30 rabbits. Two polymers (“A”, poly (lactic-co-glycolic acid) and “B”, polylactic acid), and three doses (“Low”, “Medium” and “High”) of RA (groups: AL, AM, AH, BL, BM, BH) were used on cobalt chromium stents (Rontis Corporation), one group of bare stent (C), one group (D) of Everolimus eluting stent (Xience-Pro, Abbot Vascular), and two groups of Rontis Everolimus eluting stents coated with polymer A (EA) and B (EB). Treated arteries were explanted after 4 weeks, processed by methyl methacrylate resin and evaluated by histopathology. None of the implanted stents was related with thrombus formation or extensive inflammation. Image analysis showed limited differences between groups regarding area stenosis (BH, D and EB groups had the lower values). Group BH had lower intimal mean thickness than AH (105.1 vs 75.3 μm, p = 0.024). Stents eluting RA, a non-cytotoxic drug, were not related with thrombus formation and had an acceptable degree of stenosis 4 weeks post implantation. RA dose and type of polymer may play role in the biocompatibility of the stents. © 2022, The Author(s)

Histopathological evaluation of a retinoic acid eluting stent in a rabbit iliac artery model

This study aimed to evaluate the safety and efficacy of innovative retinoic acid (RA) eluting stents with bioabsorbable polymer. Sixty stents divided in ten groups were implanted in the iliac arteries of 30 rabbits. Two polymers (“A”, poly (lactic-co-glycolic acid) and “B”, polylactic acid), and three doses (“Low”, “Medium” and “High”) of RA (groups: AL, AM, AH, BL, BM, BH) were used on cobalt chromium stents (Rontis Corporation), one group of bare stent (C), one group (D) of Everolimus eluting stent (Xience-Pro, Abbot Vascular), and two groups of Rontis Everolimus eluting stents coated with polymer A (EA) and B (EB). Treated arteries were explanted after 4 weeks, processed by methyl methacrylate resin and evaluated by histopathology. None of the implanted stents was related with thrombus formation or extensive inflammation. Image analysis showed limited differences between groups regarding area stenosis (BH, D and EB groups had the lower values). Group BH had lower intimal mean thickness than AH (105.1 vs 75.3 μm, p = 0.024). Stents eluting RA, a non-cytotoxic drug, were not related with thrombus formation and had an acceptable degree of stenosis 4 weeks post implantation. RA dose and type of polymer may play role in the biocompatibility of the stents

Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer

PURPOSE: Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing of patients. We assessed the frequency of mutations in 17 predisposition genes, including BRCA1 and BRCA2, in a large cohort of patients with triple-negative breast cancer (TNBC) unselected for family history of breast or ovarian cancer to determine the utility of germline genetic testing for those with TNBC.PATIENTS AND METHODS:Patients with TNBC (N = 1,824) unselected for family history of breast or ovarian cancer were recruited through 12 studies, and germline DNA was sequenced to identify mutations.RESULTS: Deleterious mutations were identified in 14.6% of all patients. Of these, 11.2% had mutations in the BRCA1 (8.5%) and BRCA2 (2.7%) genes. Deleterious mutations in 15 other predisposition genes were detected in 3.7% of patients, with the majority observed in genes involved in homologous recombination, including PALB2 (1.2%) and BARD1, RAD51D, RAD51C, and BRIP1 (0.3% to 0.5%). Patients with TNBC with mutations were diagnosed at an earlier age (P < .001) and had higher-grade tumors (P = .01) than those without mutations.CONCLUSION: Deleterious mutations in predisposition genes are present at high frequency in patients with TNBC unselected for family history of cancer. Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCA2. Although mutations in other predisposition genes are observed among patients with TNBC, better cancer risk estimates are needed before these mutations are used for clinical risk assessment in relatives