The Experts below are selected from a list of 1257 Experts worldwide ranked by ideXlab platform
Ranjit Manchanda - One of the best experts on this subject based on the ideXlab platform.
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cost effectiveness of population based brca1 brca2 rad51c rad51d BRIP1 palb2 mutation testing in unselected general population women
Journal of the National Cancer Institute, 2018Co-Authors: Shreeya Patel, Vladimir S Gordeev, Antonis C Antoniou, Shantel Smith, Ranjit Manchanda, John L. Hopper, Robert J MacinnisAbstract:Background: The cost-effectiveness of population-based panel testing for high- and moderate-penetrance ovarian cancer (OC)/breast cancer (BC) gene mutations is unknown. We evaluate the cost-effectiveness of population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutation testing compared with clinical criteria/family history (FH) testing in unselected general population women. Methods: A decision-analytic model comparing lifetime costs and effects of criteria/FH-based BRCA1/BRCA2 testing is compared with BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing in those fulfilling clinical criteria/strong FH of cancer (≥10% BRCA1/BRCA2 probability) and all women age 30 years or older. Analyses are presented for UK and US populations. Identified carriers undergo risk-reducing salpingo-oophorectomy. BRCA1/BRCA2/PALB2 carriers can opt for magnetic resonance imaging/mammography, chemoprevention, or risk-reducing mastectomy. One-way and probabilistic sensitivity analysis (PSA) enabled model uncertainty evaluation. Outcomes include OC, BC, and additional heart disease deaths. Quality-adjusted life-years (QALYs), OC incidence, BC incidence, and incremental cost-effectiveness ratio (ICER) were calculated. The time horizon is lifetime and perspective is payer. Results: Compared with clinical criteria/FH-based BRCA1/BRCA2 testing, clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is cost-effective (ICER = £7629.65/QALY or $49 282.19/QALY; 0.04 days' life-expectancy gained). Population-based testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutations is the most cost-effective strategy compared with current policy: ICER = £21 599.96/QALY or $54 769.78/QALY (9.34 or 7.57 days' life-expectancy gained). At £30 000/QALY and $100 000/QALY willingness-to-pay thresholds, population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 panel testing is the preferred strategy in 83.7% and 92.7% of PSA simulations; criteria/FH-based panel testing is preferred in 16.2% and 5.8% of simulations, respectively. Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing can prevent 1.86%/1.91% of BC and 3.2%/4.88% of OC in UK/US women: 657/655 OC cases and 2420/2386 BC cases prevented per million. Conclusions: Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than any clinical criteria/FH-based strategy. Clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than BRCA1/BRCA2 testing alone.
Gina G. Turrigiano - One of the best experts on this subject based on the ideXlab platform.
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activity dependent synaptic grip1 accumulation drives synaptic scaling up in response to action potential blockade
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Margaret A Gainey, Marc Nahmani, Vedakumar Tatavarty, Gina G. TurrigianoAbstract:Synaptic scaling is a form of homeostatic plasticity that stabilizes neuronal firing in response to changes in synapse number and strength. Scaling up in response to action-potential blockade is accomplished through increased synaptic accumulation of GluA2-containing AMPA receptors (AMPAR), but the receptor trafficking steps that drive this process remain largely obscure. Here, we show that the AMPAR-binding protein glutamate receptor-interacting protein-1 (GRIP1) is essential for regulated synaptic AMPAR accumulation during scaling up. Synaptic abundance of GRIP1 was enhanced by activity deprivation, directly increasing synaptic GRIP1 abundance through overexpression increased the amplitude of AMPA miniature excitatory postsynaptic currents (mEPSCs), and shRNA-mediated GRIP1 knockdown prevented scaling up of AMPA mEPSCs. Furthermore, knockdown and replace experiments targeting either GRIP1 or GluA2 revealed that scaling up requires the interaction between GRIP1 and GluA2. Finally, GRIP1 synaptic accumulation during scaling up did not require GluA2 binding. Taken together, our data support a model in which activity-dependent trafficking of GRIP1 to synaptic sites drives the forward trafficking and enhanced synaptic accumulation of GluA2-containing AMPAR during synaptic scaling up.
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activity dependent synaptic grip1 accumulation drives synaptic scaling up in response to action potential blockade
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Margaret A Gainey, Marc Nahmani, Vedakumar Tatavarty, Gina G. TurrigianoAbstract:Synaptic scaling is a form of homeostatic plasticity that stabilizes neuronal firing in response to changes in synapse number and strength. Scaling up in response to action-potential blockade is accomplished through increased synaptic accumulation of GluA2-containing AMPA receptors (AMPAR), but the receptor trafficking steps that drive this process remain largely obscure. Here, we show that the AMPAR-binding protein glutamate receptor-interacting protein-1 (GRIP1) is essential for regulated synaptic AMPAR accumulation during scaling up. Synaptic abundance of GRIP1 was enhanced by activity deprivation, directly increasing synaptic GRIP1 abundance through overexpression increased the amplitude of AMPA miniature excitatory postsynaptic currents (mEPSCs), and shRNA-mediated GRIP1 knockdown prevented scaling up of AMPA mEPSCs. Furthermore, knockdown and replace experiments targeting either GRIP1 or GluA2 revealed that scaling up requires the interaction between GRIP1 and GluA2. Finally, GRIP1 synaptic accumulation during scaling up did not require GluA2 binding. Taken together, our data support a model in which activity-dependent trafficking of GRIP1 to synaptic sites drives the forward trafficking and enhanced synaptic accumulation of GluA2-containing AMPAR during synaptic scaling up.
Robert J Macinnis - One of the best experts on this subject based on the ideXlab platform.
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cost effectiveness of population based brca1 brca2 rad51c rad51d BRIP1 palb2 mutation testing in unselected general population women
Journal of the National Cancer Institute, 2018Co-Authors: Shreeya Patel, Vladimir S Gordeev, Antonis C Antoniou, Shantel Smith, Ranjit Manchanda, John L. Hopper, Robert J MacinnisAbstract:Background: The cost-effectiveness of population-based panel testing for high- and moderate-penetrance ovarian cancer (OC)/breast cancer (BC) gene mutations is unknown. We evaluate the cost-effectiveness of population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutation testing compared with clinical criteria/family history (FH) testing in unselected general population women. Methods: A decision-analytic model comparing lifetime costs and effects of criteria/FH-based BRCA1/BRCA2 testing is compared with BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing in those fulfilling clinical criteria/strong FH of cancer (≥10% BRCA1/BRCA2 probability) and all women age 30 years or older. Analyses are presented for UK and US populations. Identified carriers undergo risk-reducing salpingo-oophorectomy. BRCA1/BRCA2/PALB2 carriers can opt for magnetic resonance imaging/mammography, chemoprevention, or risk-reducing mastectomy. One-way and probabilistic sensitivity analysis (PSA) enabled model uncertainty evaluation. Outcomes include OC, BC, and additional heart disease deaths. Quality-adjusted life-years (QALYs), OC incidence, BC incidence, and incremental cost-effectiveness ratio (ICER) were calculated. The time horizon is lifetime and perspective is payer. Results: Compared with clinical criteria/FH-based BRCA1/BRCA2 testing, clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is cost-effective (ICER = £7629.65/QALY or $49 282.19/QALY; 0.04 days' life-expectancy gained). Population-based testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutations is the most cost-effective strategy compared with current policy: ICER = £21 599.96/QALY or $54 769.78/QALY (9.34 or 7.57 days' life-expectancy gained). At £30 000/QALY and $100 000/QALY willingness-to-pay thresholds, population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 panel testing is the preferred strategy in 83.7% and 92.7% of PSA simulations; criteria/FH-based panel testing is preferred in 16.2% and 5.8% of simulations, respectively. Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing can prevent 1.86%/1.91% of BC and 3.2%/4.88% of OC in UK/US women: 657/655 OC cases and 2420/2386 BC cases prevented per million. Conclusions: Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than any clinical criteria/FH-based strategy. Clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than BRCA1/BRCA2 testing alone.
Kathleen A. Cooney - One of the best experts on this subject based on the ideXlab platform.
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absence of truncating BRIP1 mutations in chromosome 17q linked hereditary prostate cancer families
British Journal of Cancer, 2009Co-Authors: Kimberly A Zuhlke, Julie A Douglas, Ethan M Lange, Gregory R. Johnson, Albert M. Levin, Kathleen A. CooneyAbstract:Absence of truncating BRIP1 mutations in chromosome 17q-linked hereditary prostate cancer families
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truncating BRIP1 mutations are uncommon in 17q linked hereditary prostate cancer families
Cancer Research, 2008Co-Authors: Anna M Ray, Kimberly A Zuhlke, Julie A Douglas, Albert M. Levin, Gregory Johnson, Kathleen A. CooneyAbstract:3114 In a genome-wide scan (GWS) of 175 multiplex prostate cancer (PCa) families from the University of Michigan Prostate Cancer Genetics Project (PCGP), linkage was observed to markers on chromosome 17q21-24, a region which includes two breast cancer susceptibility genes, BRCA1 and BRIP1. BRIP1 is a Fanconi anemia gene (FANCJ) whose protein binds directly to the BRCT domain of BRCA1 and plays a role in DNA damage repair. Like BRCA1, germline, protein truncating mutations in BRIP1 have been identified in hereditary breast and ovarian cancer families and confer an increased risk of breast cancer to carriers. Here we examine the role of BRIP1 mutations in hereditary PCa. All BRIP1 exons and intron/exon boundaries were directly sequenced in 1 individual from each of 94 PCGP families displaying linkage (non-parametric linkage score > 0) to chromosome 17q. These families had an average of 4.1 confirmed PCa cases per family (range = 2-14), and the mean age of PCa diagnosis of confirmed cases within a pedigree was 63.7 years (range = 45.7-78.3). Thirty-seven of the 94 families contained at least 1 breast cancer (BrCa) case, and 8 families contained at least 1 ovarian cancer case. The individuals sequenced included 88 men with PCa and 6 women with BrCa. No protein truncating mutations were identified in any of the individuals sequenced. However, 24 single nucleotide polymorphisms (SNPs) including 7 missense mutations were observed; 3 of these missense mutations were previously unreported in dbSNP, and 2 of the 7 were predicted to be deleterious to the protein by both SIFT and PolyPhen. Overall, no individual was wild type at all 24 SNPs, and 59 individuals had at least one missense mutation. One individual was heterozygous for 3 different missense variants. The data presented here suggest that BRIP1 truncating mutations are not common PCa susceptibility mutations and do not account for the linkage to chromosome 17q observed in the PCGP GWS. Note that these same individuals from the 17q-linked families were previously screened for BRCA1 mutations. Only one BRCA1 truncating mutation was identified, but several missense BRCA1 variants were detected. Additional investigation is underway to determine the significance of the observed BRCA1 and BRIP1 missense mutations in hereditary PCa.
Shreeya Patel - One of the best experts on this subject based on the ideXlab platform.
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cost effectiveness of population based brca1 brca2 rad51c rad51d BRIP1 palb2 mutation testing in unselected general population women
Journal of the National Cancer Institute, 2018Co-Authors: Shreeya Patel, Vladimir S Gordeev, Antonis C Antoniou, Shantel Smith, Ranjit Manchanda, John L. Hopper, Robert J MacinnisAbstract:Background: The cost-effectiveness of population-based panel testing for high- and moderate-penetrance ovarian cancer (OC)/breast cancer (BC) gene mutations is unknown. We evaluate the cost-effectiveness of population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutation testing compared with clinical criteria/family history (FH) testing in unselected general population women. Methods: A decision-analytic model comparing lifetime costs and effects of criteria/FH-based BRCA1/BRCA2 testing is compared with BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing in those fulfilling clinical criteria/strong FH of cancer (≥10% BRCA1/BRCA2 probability) and all women age 30 years or older. Analyses are presented for UK and US populations. Identified carriers undergo risk-reducing salpingo-oophorectomy. BRCA1/BRCA2/PALB2 carriers can opt for magnetic resonance imaging/mammography, chemoprevention, or risk-reducing mastectomy. One-way and probabilistic sensitivity analysis (PSA) enabled model uncertainty evaluation. Outcomes include OC, BC, and additional heart disease deaths. Quality-adjusted life-years (QALYs), OC incidence, BC incidence, and incremental cost-effectiveness ratio (ICER) were calculated. The time horizon is lifetime and perspective is payer. Results: Compared with clinical criteria/FH-based BRCA1/BRCA2 testing, clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is cost-effective (ICER = £7629.65/QALY or $49 282.19/QALY; 0.04 days' life-expectancy gained). Population-based testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutations is the most cost-effective strategy compared with current policy: ICER = £21 599.96/QALY or $54 769.78/QALY (9.34 or 7.57 days' life-expectancy gained). At £30 000/QALY and $100 000/QALY willingness-to-pay thresholds, population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 panel testing is the preferred strategy in 83.7% and 92.7% of PSA simulations; criteria/FH-based panel testing is preferred in 16.2% and 5.8% of simulations, respectively. Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing can prevent 1.86%/1.91% of BC and 3.2%/4.88% of OC in UK/US women: 657/655 OC cases and 2420/2386 BC cases prevented per million. Conclusions: Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than any clinical criteria/FH-based strategy. Clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than BRCA1/BRCA2 testing alone.