نتائج البحث - "Garsed, Dale W."

الوصف: Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, and drivers of ITH across cancer types are poorly understood. To address this, we extensively characterize ITH across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types. Nearly all informative samples (95.1%) contain evidence of distinct subclonal expansions with frequent branching relationships between subclones. We observe positive selection of subclonal driver mutations across most cancer types and identify cancer type-specific subclonal patterns of driver gene mutations, fusions, structural variants, and copy number alterations as well as dynamic changes in mutational processes between subclonal expansions. Our results underline the importance of ITH and its drivers in tumor evolution and provide a pan-cancer resource of comprehensively annotated subclonal events from whole-genome sequencing data.

URL الوصول: https://escholarship.org/uc/item/6h7872p6

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Author Correction: Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities

المؤلفون: Bateman, Nicholas W.^{Aff1, Aff2, Aff3, IDs41698024005889_cor1}, Abulez, Tamara^{Aff1, Aff2}, Soltis, Anthony R., McPherson, Andrew, Choi, Seongmin, Garsed, Dale W.^{Aff6, Aff7}, Pandey, Ahwan, Tian, Chunqiao^{Aff1, Aff2}, Hood, Brian L.^{Aff1, Aff2}, Conrads, Kelly A.^{Aff1, Aff2}, Teng, Pang-ning^{Aff1, Aff2}, Oliver, Julie^{Aff1, Aff2}, Gist, Glenn^{Aff1, Aff2}, Mitchell, Dave^{Aff1, Aff2}, Litzi, Tracy J.^{Aff1, Aff2}, Tarney, Christopher M., Crothers, Barbara A., Mhawech-Fauceglia, Paulette, Dalgard, Clifton L., Wilkerson, Matthew D., Pierobon, Mariaelena, Petricoin, Emanuel F., Yan, Chunhua, Meerzaman, Daoud, Bodelon, Clara, Wentzensen, Nicolas, Lee, Jerry S. H., Huntsman, David G., Shah, Sohrab, Shriver, Craig D., Phippen, Neil T., Darcy, Kathleen M.^{Aff1, Aff2, Aff3}, Bowtell, David D. L.^{Aff6, Aff7}, Conrads, Thomas P.^{Aff1, Aff3, Aff15, IDs41698024005889_cor35}, Maxwell, G. Larry^{Aff1, Aff3, Aff15, IDs41698024005889_cor36}

المصدر: npj Precision Oncology. 8(1)

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Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities

المؤلفون: Bateman, Nicholas W.^{Aff1, Aff2, Aff3, IDs41698024005198_cor1}, Abulez, Tamara^{Aff1, Aff2}, Soltis, Anthony R., McPherson, Andrew, Choi, Seongmin, Garsed, Dale W.^{Aff6, Aff7}, Pandey, Ahwan, Tian, Chunqiao^{Aff1, Aff2}, Hood, Brian L.^{Aff1, Aff2}, Conrads, Kelly A.^{Aff1, Aff2}, Teng, Pang-ning^{Aff1, Aff2}, Oliver, Julie^{Aff1, Aff2}, Gist, Glenn^{Aff1, Aff2}, Mitchell, Dave^{Aff1, Aff2}, Litzi, Tracy J.^{Aff1, Aff2}, Tarney, Christopher M., Crothers, Barbara A., Mhawech-Fauceglia, Paulette, Dalgard, Clifton L., Wilkerson, Matthew D., Pierobon, Mariaelena, Petricoin, Emanuel F., Yan, Chunhua, Meerzaman, Daoud, Bodelon, Clara, Wentzensen, Nicolas, Lee, Jerry S. H., Huntsman, David G., Shah, Sohrab, Shriver, Craig D., Phippen, Neil T., Darcy, Kathleen M.^{Aff1, Aff2, Aff3}, Bowtell, David D. L.^{Aff6, Aff7}, Conrads, Thomas P.^{Aff1, Aff3, Aff15, IDs41698024005198_cor35}, Maxwell, G. Larry^{Aff1, Aff3, Aff15, IDs41698024005198_cor36}

المصدر: npj Precision Oncology. 8(1)

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Menopausal hormone therapy prior to the diagnosis of ovarian cancer is associated with improved survival

المؤلفون: Brieger, Katharine K, Peterson, Siri, Lee, Alice W, Mukherjee, Bhramar, Bakulski, Kelly M, Alimujiang, Aliya, Anton-Culver, Hoda, Anglesio, Michael S, Bandera, Elisa V, Berchuck, Andrew, Bowtell, David DL, Chenevix-Trench, Georgia, Cho, Kathleen R, Cramer, Daniel W, DeFazio, Anna, Doherty, Jennifer A, Fortner, Renée T, Garsed, Dale W, Gayther, Simon A, Gentry-Maharaj, Aleksandra, Goode, Ellen L, Goodman, Marc T, Harris, Holly R, Høgdall, Estrid, Huntsman, David G, Shen, Hui, Jensen, Allan, Johnatty, Sharon E, Jordan, Susan J, Kjaer, Susanne K, Kupryjanczyk, Jolanta, Lambrechts, Diether, McLean, Karen, Menon, Usha, Modugno, Francesmary, Moysich, Kirsten, Ness, Roberta, Ramus, Susan J, Richardson, Jean, Risch, Harvey, Rossing, Mary Anne, Trabert, Britton, Wentzensen, Nicolas, Ziogas, Argyrios, Terry, Kathryn L, Wu, Anna H, Hanley, Gillian E, Pharoah, Paul, Webb, Penelope M, Pike, Malcolm C, Pearce, Celeste Leigh, Consortium, for the Ovarian Cancer Association

المصدر: Gynecologic Oncology. 158(3)

الوصف: PurposePrior studies of menopausal hormone therapy (MHT) and ovarian cancer survival have been limited by lack of hormone regimen detail and insufficient sample sizes. To address these limitations, a comprehensive analysis of 6419 post-menopausal women with pathologically confirmed ovarian carcinoma was conducted to examine the association between MHT use prior to diagnosis and survival.MethodsData from 15 studies in the Ovarian Cancer Association Consortium were included. MHT use was examined by type (estrogen-only (ET) or estrogen+progestin (EPT)), duration, and recency of use relative to diagnosis. Cox proportional hazards models were used to estimate the association between hormone therapy use and survival. Logistic regression and mediation analysis was used to explore the relationship between MHT use and residual disease following debulking surgery.ResultsUse of ET or EPT for at least five years prior to diagnosis was associated with better ovarian cancer survival (hazard ratio, 0.80; 95% CI, 0.74 to 0.87). Among women with advanced stage, high-grade serous carcinoma, those who used MHT were less likely to have any macroscopic residual disease at the time of primary debulking surgery (p for trend

وصف الملف: application/pdf

URL الوصول: https://escholarship.org/uc/item/4bf0w483

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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes

المؤلفون: Rheinbay, Esther, Nielsen, Morten Muhlig, Abascal, Federico, Wala, Jeremiah A., Shapira, Ofer, Tiao, Grace, Hornshoj, Henrik, Hess, Julian M., Juul, Randi Istrup, Lin, Ziao, Feuerbach, Lars, Sabarinathan, Radhakrishnan, Madsen, Tobias, Kim, Jaegil, Mularoni, Loris, Shuai, Shimin, Lanzos, Andres, Herrmann, Carl, Maruvka, Yosef E., Shen, Ciyue, Amin, Samirkumar B., Bandopadhayay, Pratiti, Bertl, Johanna, Boroevich, Keith A., Busanovich, John, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Craft, David, Dhingra, Priyanka, Diamanti, Klev, 1987, Fonseca, Nuno A., Gonzalez-Perez, Abel, Guo, Qianyun, Hamilton, Mark P., Haradhvala, Nicholas J., Hong, Chen, Isaev, Keren, Johnson, Todd A., Juul, Malene, Kahles, Andre, Kahraman, Abdullah, Kim, Youngwook, Komorowski, Jan, Kumar, Kiran, Kumar, Sushant, Lee, Donghoon, Lehmann, Kjong-Van, Li, Yilong, Liu, Eric Minwei, Lochovsky, Lucas, Park, Keunchil, Pich, Oriol, Roberts, Nicola D., Saksena, Gordon, Schumacher, Steven E., Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stewart, Chip, Tamborero, David, Tubio, Jose M. C., Umer, Husen Muhammad, Uuskula-Reimand, Liis, Wadelius, Claes, 1955, Wadi, Lina, Yao, Xiaotong, Zhang, Cheng-Zhong, Zhang, Jing, Haber, James E., Hobolth, Asger, Imielinski, Marcin, Kellis, Manolis, Lawrence, Michael S., von Mering, Christian, Nakagawa, Hidewaki, Raphael, Benjamin J., Rubin, Mark A., Sander, Chris, Stein, Lincoln D., Stuart, Joshua M., Tsunoda, Tatsuhiko, Wheeler, David A., Johnson, Rory, Reimand, Juri, Gerstein, Mark, Khurana, Ekta, Campbell, Peter J., Lopez-Bigas, Nuria, Weischenfeldt, Joachim, Beroukhim, Rameen, Martincorena, Inigo, Pedersen, Jakob Skou, Getz, Gad, Bader, Gary D., Barenboim, Jonathan, Brunak, Soren, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Fink, J. Lynn, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W., Gut, Ivo G., Haan, David, Harmanci, Arif O., Helmy, Mohamed, Hodzic, Ermin, Izarzugaza, Jose M. G., Kim, Jong K., Korbel, Jan O., Larsson, Erik, Li, Shantao, Li, Xiaotong, Lou, Shaoke, Marchal, Kathleen, Martinez-Fundichely, Alexander, McGillivray, Patrick D., Meyerson, William, Muinos, Ferran, Paczkowska, Marta, Park, Kiejung, Pons, Tirso, Pulido-Tamayo, Sergio, Reyes-Salazar, Iker, Reyna, Matthew A., Rubio-Perez, Carlota, Sahinalp, S. Cenk, Salichos, Leonidas, Shackleton, Mark, Shrestha, Raunak, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven P. C., Wang, Jiayin, Warrell, Jonathan, Waszak, Sebastian M., Wu, Guanming, Yu, Jun, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, Akdemir, Kadir C., Alvarez, Eva G., Baez-Ortega, Adrian, Boutros, Paul C., Bowtell, David D. L., Brors, Benedikt, Burns, Kathleen H., Chan, Kin, CortesCiriano, Isidro, Dueso-Barroso, Ana, Dunford, Andrew J., Edwards, Paul A., Estivill, Xavier, Etemadmoghadam, Dariush, Frenkel-Morgenstern, Milana, Gordenin, Dmitry A., Hutter, Barbara, Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Klimczak, Leszek J., Koh, Youngil, Lee, Eunjung Alice, Lee, Jake June-Koo, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Meyerson, Matthew, Miyano, Satoru, Navarro, Fabio C. P., Ossowski, Stephan, Park, Peter J., Pearson, John, V, Puiggros, Montserrat, Rippe, Karsten, Roberts, Steven A., RodriguezMartin, Bernardo, Scully, Ralph, Torrents, David, Villasante, Izar, Waddell, Nicola, Yang, Lixing, Yoon, Sung-Soo, Zamora, Jorge

المصدر: Nature. 578(7793):102-111

الوصف: The discovery of drivers of cancer has traditionally focused on protein-coding genes(1-4). Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium(5) of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers(6,7), raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.

وصف الملف: electronic

URL الوصول: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-412969
https://doi.org/10.1038/s41586-020-1965-x
https://uu.diva-portal.org/smash/get/diva2:1444508/FULLTEXT01.pdf

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Homologous recombination proficient subtypes of highgrade serous ovarian cancer: treatment options for a poor prognosis group.

المؤلفون: Stiegeler, Nadja, Garsed, Dale W., Au-Yeung, George, Bowtell, David D. L., Heinzelmann-Schwarz, Viola, Zwimpfer, Tibor A.

المصدر: Frontiers in Oncology; 2024, p1-21, 20p

مصطلحات موضوعية: HOMOLOGOUS recombination, OVARIAN cancer, DNA repair, PROGNOSIS, CANCER treatment, OVARIAN epithelial cancer

مستخلص: Approximately 50% of tubo-ovarian high-grade serous carcinomas (HGSCs) have functional homologous recombination-mediated (HR) DNA repair, so-called HR-proficient tumors, which are often associated with primary platinum resistance (relapse within six months after completion of first-line therapy), minimal benefit from poly(ADP-ribose) polymerase (PARP) inhibitors, and shorter survival. HR-proficient tumors comprise multiple molecular subtypes including cases with CCNE1 amplification, AKT2 amplification or CDK12 alteration, and are often characterized as "cold" tumors with fewer infiltrating lymphocytes and decreased expression of PD-1/PD-L1. Several new treatment approaches aim to manipulate these negative prognostic features and render HR-proficient tumors more susceptible to treatment. Alterations in multiple different molecules and pathways in the DNA damage response are driving new drug development to target HR-proficient cancer cells, such as inhibitors of the CDK or P13K/AKT pathways, as well as ATR inhibitors. Treatment combinations with chemotherapy or PARP inhibitors and agents targeting DNA replication stress have shown promising preclinical and clinical results. New approaches in immunotherapy are also being explored, including vaccines or antibody drug conjugates. Many approaches are still in the early stages of development and further clinical trials will determine their clinical relevance. There is a need to include HR-proficient tumors in ovarian cancer trials and to analyze them in a more targeted manner to provide further evidence for their specific therapy, as this will be crucial in improving the overall prognosis of HGSC and ovarian cancer in general. [ABSTRACT FROM AUTHOR]

: Copyright of Frontiers in Oncology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis

المؤلفون: Carlevaro-Fita, Joana, Lanzos, Andres, Feuerbach, Lars, Hong, Chen, Mas-Ponte, David, Pedersen, Jakob Skou, Johnson, Rory, Abascal, Federico, Amin, Samirkumar B., Bader, Gary D., Barenboim, Jonathan, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A., Brunak, Soren, Campbell, Peter J., Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, 1987, Fink, J. Lynn, Fonseca, Nuno A., Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W., Gerstein, Mark, Getz, Gad, Gonzalez-Perez, Abel, Guo, Qianyun, Gut, Ivo G., Haan, David, Hamilton, Mark P., Haradhvala, Nicholas J., Harmanci, Arif O., Helmy, Mohamed, Herrmann, Carl, Hess, Julian M., Hobolth, Asger, Hodzic, Ermin, Hornshoj, Henrik, Isaev, Keren, Izarzugaza, Jose M. G., Johnson, Todd A., Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K., Kim, Youngwook, Komorowski, Jan, Korbel, Jan O., Kumar, Sushant, Larsson, Erik, Lawrence, Michael S., Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Inigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E., McGillivray, Patrick D., Meyerson, William, Muinos, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pich, Oriol, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J., Reimand, Juri, Reyes-Salazar, Iker, Reyna, Matthew A., Rheinbay, Esther, Rubin, Mark A., Rubio-Perez, Carlota, Sabarinathan, Radhakrishnan, Sahinalp, S. Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E., Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D., Stuart, Joshua M., Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen Muhammad, Uuskula-Reimand, Liis, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven P. C., Wadelius, Claes, 1955, Wadi, Lina, Wang, Jiayin, Warrell, Jonathan, Waszak, Sebastian M., Weischenfeldt, Joachim, Wheeler, David A., Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, von Mering, Christian

المصدر: Communications Biology. 3(1)

الوصف: Joana Carlevaro-Fita, Andres Lanzos et al. present the Cancer LncRNA Census (CLC), a manually curated dataset of 122 long noncoding RNAs (lncRNAs) with experimentally-validated functions in cancer based on data from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. CLC lncRNAs have unique gene features, and a number display evidence for cancer-driving functions that are conserved from humans to mice. Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.

وصف الملف: electronic

URL الوصول: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-407981
https://doi.org/10.1038/s42003-019-0741-7
https://uu.diva-portal.org/smash/get/diva2:1421214/FULLTEXT01.pdf

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