Search

Your search keyword '"Murtaza, Muhammed"' showing total 235 results
Start Over Author "Murtaza, Muhammed"
235 results on '"Murtaza, Muhammed"'

2. Genome-wide analysis of aberrant position and sequence of plasma DNA fragment ends in patients with cancer.

Author

Budhraja, Karan, McDonald, Bradon, Stephens, Michelle, Contente-Cuomo, Tania, Markus, Havell, Farooq, Maria, Favaro, Patricia, Connor, Sydney, Byron, Sara, Egan, Jan, Ernst, Brenda, McDaniel, Timothy, Sekulic, Aleksandar, Tran, Nhan, Prados, Michael, Borad, Mitesh, Berens, Michael, Pockaj, Barbara, LoRusso, Patricia, Bryce, Alan, Trent, Jeffrey, and Murtaza, Muhammed

Subjects
Humans, DNA, Neoplasms, Cell-Free Nucleic Acids, Chromatin, Nucleotides, Biomarkers, Tumor, Sequence Analysis, DNA
Abstract

Genome-wide fragmentation patterns in cell-free DNA (cfDNA) in plasma are strongly influenced by cellular origin due to variation in chromatin accessibility across cell types. Such differences between healthy and cancer cells provide the opportunity for development of novel cancer diagnostics. Here, we investigated whether analysis of cfDNA fragment end positions and their surrounding DNA sequences reveals the presence of tumor-derived DNA in blood. We performed genome-wide analysis of cfDNA from 521 samples and analyzed sequencing data from an additional 2147 samples, including healthy individuals and patients with 11 different cancer types. We developed a metric based on genome-wide differences in fragment positioning, weighted by fragment length and GC content [information-weighted fraction of aberrant fragments (iwFAF)]. We observed that iwFAF strongly correlated with tumor fraction, was higher for DNA fragments carrying somatic mutations, and was higher within genomic regions affected by copy number amplifications. We also calculated sample-level means of nucleotide frequencies observed at genomic positions spanning fragment ends. Using a combination of iwFAF and nine nucleotide frequencies from three positions surrounding fragment ends, we developed a machine learning model to differentiate healthy individuals from patients with cancer. We observed an area under the receiver operative characteristic curve (AUC) of 0.91 for detection of cancer at any stage and an AUC of 0.87 for detection of stage I cancer. Our findings remained robust with as few as 1 million fragments analyzed per sample, demonstrating that analysis of fragment ends can become a cost-effective and accessible approach for cancer detection and monitoring.

Published
2023

5. ASO Visual Abstract: Association of Neighborhood Disadvantage with Short- and Long-Term Outcomes After Pancreatectomy for Pancreatic Ductal Adenocarcinoma

Author

Marcinak, Clayton T., Praska, Corinne E., Vidri, Roberto J., Taylor, Amy K., Krebsbach, John K., Ahmed, Kaleem S., LoConte, Noelle K., Varley, Patrick R., Afshar, Majid, Weber, Sharon M., Abbott, Daniel E., Mathew, Jomol, Murtaza, Muhammed, Burkard, Mark E., Churpek, Matthew M., and Zafar, Syed Nabeel

Published
2024
Full Text
View/download PDF

6. Circulating tumor DNA as an early cancer detection tool

Author

Campos-Carrillo, Andrea, Weitzel, Jeffrey N, Sahoo, Prativa, Rockne, Russell, Mokhnatkin, Janet V, Murtaza, Muhammed, Gray, Stacy W, Goetz, Laura, Goel, Ajay, Schork, Nicholas, and Slavin, Thomas P

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Women's Health, Cancer Genomics, Cancer, Genetics, Prevention, Health Services, Genetic Testing, Human Genome, Clinical Research, Rare Diseases, Digestive Diseases, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Good Health and Well Being, Animals, Circulating Tumor DNA, Early Detection of Cancer, Humans, Neoplasms, Circulating tumor DNA, Early detection, Cell-free DNA, Cancer screening, Cancer detection, Pharmacology and Pharmaceutical Sciences, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

Circulating tumor DNA holds substantial promise as an early detection biomarker, particularly for cancers that do not have currently accepted screening methodologies, such as ovarian, pancreatic, and gastric cancers. Many features intrinsic to ctDNA analysis may be leveraged to enhance its use as an early cancer detection biomarker: including ctDNA fragment lengths, DNA copy number variations, and associated patient phenotypic information. Furthermore, ctDNA testing may be synergistically used with other multi-omic biomarkers to enhance early detection. For instance, assays may incorporate early detection proteins (i.e., CA-125), epigenetic markers, circulating tumor RNA, nucleosomes, exosomes, and associated immune markers. Many companies are currently competing to develop a marketable early cancer detection test that leverages ctDNA. Although some hurdles (like early stage disease assay accuracy, high implementation costs, confounding from clonal hematopoiesis, and lack of clinical utility studies) need to be addressed before integration into healthcare, ctDNA assays hold substantial potential as an early cancer screening test.

Published
2020

9. Evaluation of pre-analytical factors affecting plasma DNA analysis.

Author

Markus, Havell, Contente-Cuomo, Tania, Farooq, Maria, Liang, Winnie S, Borad, Mitesh J, Sivakumar, Shivan, Gollins, Simon, Tran, Nhan L, Dhruv, Harshil D, Berens, Michael E, Bryce, Alan, Sekulic, Aleksandar, Ribas, Antoni, Trent, Jeffrey M, LoRusso, Patricia M, and Murtaza, Muhammed

Subjects
Humans, Blood Specimen Collection, Polymerase Chain Reaction, Female, Male, Cell-Free Nucleic Acids
Abstract

Pre-analytical factors can significantly affect circulating cell-free DNA (cfDNA) analysis. However, there are few robust methods to rapidly assess sample quality and the impact of pre-analytical processing. To address this gap and to evaluate effects of DNA extraction methods and blood collection tubes on cfDNA yield and fragment size, we developed a multiplexed droplet digital PCR (ddPCR) assay with 5 short and 4 long amplicons targeting single copy genomic loci. Using this assay, we compared 7 cfDNA extraction kits and found cfDNA yield and fragment size vary significantly. We also compared 3 blood collection protocols using plasma samples from 23 healthy volunteers (EDTA tubes processed within 1 hour and Cell-free DNA Blood Collection Tubes processed within 24 and 72 hours) and found no significant differences in cfDNA yield, fragment size and background noise between these protocols. In 219 clinical samples, cfDNA fragments were shorter in plasma samples processed immediately after venipuncture compared to archived samples, suggesting contribution of background DNA by lysed peripheral blood cells. In summary, we have described a multiplexed ddPCR assay to assess quality of cfDNA samples prior to downstream molecular analyses and we have evaluated potential sources of pre-analytical variation in cfDNA studies.

Published
2018

11. Ultrasensitive Circulating Tumor DNA Pilot Study Distinguishes Complete Response and Partial Response With Immunotherapy in Patients With Metastatic Renal Cell Carcinoma

Author

Chehrazi-Raffle, Alexander, Muddasani, Ramya, Dizman, Nazli, Hsu, JoAnn, Meza, Luis, Zengin, Zeynep B., Malhotra, Jasnoor, Chawla, Neal, Dorff, Tanya, Contente-Cuomo, Tania, Dinwiddie, Devin, McDonald, Bradon R., McDaniel, Timothy, Trent, Jeffrey M., Baehner, Frederick L., Murtaza, Muhammed, and Pal, Sumanta K.

Published
2023
Full Text
View/download PDF

14. The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer

Author

De Mattos-Arruda, Leticia, Sammut, Stephen-John, Ross, Edith M., Bashford-Rogers, Rachael, Greenstein, Erez, Markus, Havell, Morganella, Sandro, Teng, Yvonne, Maruvka, Yosef, Pereira, Bernard, Rueda, Oscar M., Chin, Suet-Feung, Contente-Cuomo, Tania, Mayor, Regina, Arias, Alexandra, Ali, H. Raza, Cope, Wei, Tiezzi, Daniel, Dariush, Aliakbar, Dias Amarante, Tauanne, Reshef, Dan, Ciriaco, Nikaoly, Martinez-Saez, Elena, Peg, Vicente, Ramon y Cajal, Santiago, Cortes, Javier, Vassiliou, George, Getz, Gad, Nik-Zainal, Serena, Murtaza, Muhammed, Friedman, Nir, Markowetz, Florian, Seoane, Joan, and Caldas, Carlos

Published
2019
Full Text
View/download PDF

16. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height

Author

Lanktree, Matthew B, Guo, Yiran, Murtaza, Muhammed, Glessner, Joseph T, Bailey, Swneke D, Onland-Moret, N Charlotte, Lettre, Guillaume, Ongen, Halit, Rajagopalan, Ramakrishnan, Johnson, Toby, Shen, Haiqing, Nelson, Christopher P, Klopp, Norman, Baumert, Jens, Padmanabhan, Sandosh, Pankratz, Nathan, Pankow, James S, Shah, Sonia, Taylor, Kira, Barnard, John, Peters, Bas J, Maloney, Cliona M, Lobmeyer, Maximilian T, Stanton, Alice, Zafarmand, M Hadi, Romaine, Simon PR, Mehta, Amar, van Iperen, Erik PA, Gong, Yan, Price, Tom S, Smith, Erin N, Kim, Cecilia E, Li, Yun R, Asselbergs, Folkert W, Atwood, Larry D, Bailey, Kristian M, Bhatt, Deepak, Bauer, Florianne, Behr, Elijah R, Bhangale, Tushar, Boer, Jolanda MA, Boehm, Bernhard O, Bradfield, Jonathan P, Brown, Morris, Braund, Peter S, Burton, Paul R, Carty, Cara, Chandrupatla, Hareesh R, Chen, Wei, Connell, John, Dalgeorgou, Chrysoula, de Boer, Anthonius, Drenos, Fotios, Elbers, Clara C, Fang, James C, Fox, Caroline S, Frackelton, Edward C, Fuchs, Barry, Furlong, Clement E, Gibson, Quince, Gieger, Christian, Goel, Anuj, Grobbee, Diederik E, Hastie, Claire, Howard, Philip J, Huang, Guan-Hua, Johnson, W Craig, Li, Qing, Kleber, Marcus E, Klein, Barbara EK, Klein, Ronald, Kooperberg, Charles, Ky, Bonnie, LaCroix, Andrea, Lanken, Paul, Lathrop, Mark, Li, Mingyao, Marshall, Vanessa, Melander, Olle, Mentch, Frank D, Meyer, Nuala J, Monda, Keri L, Montpetit, Alexandre, Murugesan, Gurunathan, Nakayama, Karen, Nondahl, Dave, Onipinla, Abiodun, Rafelt, Suzanne, Newhouse, Stephen J, Otieno, F George, Patel, Sanjey R, Putt, Mary E, Rodriguez, Santiago, Safa, Radwan N, Sawyer, Douglas B, Schreiner, Pamela J, Simpson, Claire, Sivapalaratnam, Suthesh, Srinivasan, Sathanur R, and Suver, Christine

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adult, Black or African American, Asian People, Body Height, Cardiovascular System, Female, Gene Frequency, Genetic Heterogeneity, Genetic Loci, Genome-Wide Association Study, Hispanic or Latino, Humans, Interleukin-11, Male, Polymorphism, Single Nucleotide, Smad3 Protein, White People, Hugh Watkins on behalf of PROCARDIS, Meena Kumari on behalf of the Whitehall II Study and the WHII 50K Group, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.

Published
2011

17. ASO Visual Abstract: Association of Neighborhood Disadvantage with Short- and Long-Term Outcomes After Pancreatectomy for Pancreatic Ductal Adenocarcinoma

Author

Marcinak, Clayton T., primary, Praska, Corinne E., additional, Vidri, Roberto J., additional, Taylor, Amy K., additional, Krebsbach, John K., additional, Ahmed, Kaleem S., additional, LoConte, Noelle K., additional, Varley, Patrick R., additional, Afshar, Majid, additional, Weber, Sharon M., additional, Abbott, Daniel E., additional, Mathew, Jomol, additional, Murtaza, Muhammed, additional, Burkard, Mark E., additional, Churpek, Matthew M., additional, and Zafar, Syed Nabeel, additional

Published
2023
Full Text
View/download PDF

18. Association of Neighborhood Disadvantage with Short- and Long-Term Outcomes After Pancreatectomy for Pancreatic Ductal Adenocarcinoma

Author

Marcinak, Clayton T., primary, Praska, Corinne E., additional, Vidri, Roberto J., additional, Taylor, Amy K., additional, Krebsbach, John K., additional, Ahmed, Kaleem S., additional, LoConte, Noelle K., additional, Varley, Patrick R., additional, Afshar, Majid, additional, Weber, Sharon M., additional, Abbott, Daniel E., additional, Mathew, Jomol, additional, Murtaza, Muhammed, additional, Burkard, Mark E., additional, Churpek, Matthew M., additional, and Zafar, Syed Nabeel, additional

Published
2023
Full Text
View/download PDF

20. List of Contributors

Author

Alturkistani, Abrar, primary, An, Juanjuan, additional, Benda, Norbert, additional, Bienfait, Karina, additional, Blackler, Adele R., additional, Bøgsted, Martin, additional, Brindley, David, additional, Broich, Karl, additional, Brøndum, Rasmus F., additional, Brunhoeber, Patrick, additional, Bureau, Matthew, additional, Car, Josip, additional, Carter, Alison, additional, Clarke, Tara, additional, Clements, June, additional, Cross, Darren, additional, Doble, Brett, additional, Dolled-Filhart, Marisa, additional, Domazetoski, Elena, additional, Duncan, Mark W., additional, ElGabry, Ehab A., additional, Ellison, Aaron R., additional, Emancipator, Kenneth, additional, Enzmann, Harald, additional, Farooq, Maria, additional, Feng, Janine, additional, Foley, Kimberley, additional, Generalov, Evgenii, additional, Go, Ning Fei, additional, Goltsov, Alexey, additional, Green, George A., additional, Hersom, Maria, additional, Honarpour, Narimon, additional, Iddamalgoda, Lahiru, additional, Ikeda, Masayuki, additional, Jenkins, Suzanne, additional, Jørgensen, Jan Trøst, additional, Kapadia, Monesh, additional, Karwowska, Sylwia, additional, Kuzulugil, Sebnem S., additional, Lam, Ching, additional, Lewis, Jason S., additional, Li, Jinbo, additional, Liesenfeld, Oliver, additional, Lopes, Gilberto, additional, Luo, Dee, additional, Meinert, Edward, additional, Meyer, Ralf, additional, Mistry, Amita, additional, Mitsakakis, Nicholas, additional, Mollerup, Jens, additional, Montalto, Michael C., additional, Murata, Lauren B., additional, Murtaza, Muhammed, additional, Nielsen, Karsten Bork, additional, Pant, Saumya, additional, Parker, Jayson L., additional, Pereira, Patrícia M.R., additional, Ramarao, Manjunath, additional, Rigl, Ted, additional, Schildgen, Oliver, additional, Schildgen, Verena, additional, Scholl, Catharina, additional, Scudder, Sidney A., additional, Seyfried, Donna, additional, Sharma, Abha, additional, Shimazawa, Rumiko, additional, Simon, Richard, additional, Singh, Shalini, additional, Sobol, Nicholas B., additional, Stanforth, David A., additional, Stingl, Julia, additional, Sundararajan, Vijayaraghava Seshadri, additional, Suravajhala, Prashanth, additional, Tosolini, Alessandra, additional, Tsou, Jeff, additional, Tully, Kathryn M., additional, Walk, Eric E., additional, Wu, Dianna, additional, Xu, Xiaolei, additional, and Yu, Karen, additional

Published
2019
Full Text
View/download PDF

22. Tables S1 to S13 from Identification of Recurrent Activating HER2 Mutations in Primary Canine Pulmonary Adenocarcinoma

Author

Lorch, Gwendolen, primary, Sivaprakasam, Karthigayini, primary, Zismann, Victoria, primary, Perdigones, Nieves, primary, Contente-Cuomo, Tania, primary, Nazareno, Alexandra, primary, Facista, Salvatore, primary, Wong, Shukmei, primary, Drenner, Kevin, primary, Liang, Winnie S., primary, Amann, Joseph M., primary, Sinicropi-Yao, Sara L., primary, Koenig, Michael J., primary, La Perle, Krista, primary, Whitsett, Timothy G., primary, Murtaza, Muhammed, primary, Trent, Jeffrey M., primary, Carbone, David P., primary, and Hendricks, William P.D., primary

Published
2023
Full Text
View/download PDF

23. Figure S2 from Identification of Recurrent Activating HER2 Mutations in Primary Canine Pulmonary Adenocarcinoma

Author

Lorch, Gwendolen, primary, Sivaprakasam, Karthigayini, primary, Zismann, Victoria, primary, Perdigones, Nieves, primary, Contente-Cuomo, Tania, primary, Nazareno, Alexandra, primary, Facista, Salvatore, primary, Wong, Shukmei, primary, Drenner, Kevin, primary, Liang, Winnie S., primary, Amann, Joseph M., primary, Sinicropi-Yao, Sara L., primary, Koenig, Michael J., primary, La Perle, Krista, primary, Whitsett, Timothy G., primary, Murtaza, Muhammed, primary, Trent, Jeffrey M., primary, Carbone, David P., primary, and Hendricks, William P.D., primary

Published
2023
Full Text
View/download PDF

24. Supplementary Legend from Identification of Recurrent Activating HER2 Mutations in Primary Canine Pulmonary Adenocarcinoma

Author

Lorch, Gwendolen, primary, Sivaprakasam, Karthigayini, primary, Zismann, Victoria, primary, Perdigones, Nieves, primary, Contente-Cuomo, Tania, primary, Nazareno, Alexandra, primary, Facista, Salvatore, primary, Wong, Shukmei, primary, Drenner, Kevin, primary, Liang, Winnie S., primary, Amann, Joseph M., primary, Sinicropi-Yao, Sara L., primary, Koenig, Michael J., primary, La Perle, Krista, primary, Whitsett, Timothy G., primary, Murtaza, Muhammed, primary, Trent, Jeffrey M., primary, Carbone, David P., primary, and Hendricks, William P.D., primary

Published
2023
Full Text
View/download PDF

28. Cancer Genomics and Evolution

Author

Hendricks, William P. D., primary, Sekulic, Aleksandar, additional, Bryce, Alan H., additional, Murtaza, Muhammed, additional, Ramos, Pilar, additional, Lang, Jessica D., additional, Whitsett, Timothy G., additional, McDaniel, Timothy K., additional, Rockne, Russell C., additional, Banovich, Nicholas, additional, and Trent, Jeffrey M., additional

Published
2022
Full Text
View/download PDF

30. Genomic landscapes of canine splenic angiosarcoma (hemangiosarcoma) contain extensive heterogeneity within and between patients

Author

Wong, Shukmei, primary, Ehrhart, E. J., additional, Stewart, Samuel, additional, Zismann, Victoria, additional, Cawley, Jacob, additional, Halperin, Rebecca, additional, Briones, Natalia, additional, Richter, Keith, additional, Sivaprakasam, Karthigayini, additional, Perdigones, Nieves, additional, Contente-Cuomo, Tania, additional, Facista, Salvatore, additional, Trent, Jeffrey M., additional, Murtaza, Muhammed, additional, Khanna, Chand, additional, and Hendricks, William P. D., additional

Published
2022
Full Text
View/download PDF

31. The Pakistan Risk of Myocardial Infarction Study: A Resource for the Study of Genetic, Lifestyle and Other Determinants of Myocardial Infarction in South Asia

Author

Saleheen, Danish, Zaidi, Moazzam, Rasheed, Asif, Ahmad, Usman, Hakeem, Abdul, Murtaza, Muhammed, Kayani, Waleed, Faruqui, Azhar, Kundi, Assadullah, Zaman, Khan Shah, Yaqoob, Zia, Cheema, Liaquat Ali, Samad, Abdus, Rasheed, Syed Zahed, Mallick, Nadeem Hayat, Azhar, Muhammad, Jooma, Rashid, Gardezi, Ali Raza, Memon, Nazir, Ghaffar, Abdul, Fazal-ur-Rehman, Khan, Nadir, Shah, Nabi, Shah, Asad Ali, Samuel, Maria, Hanif, Farina, Yameen, Madiha, Naz, Sobia, Sultana, Aisha, Nazir, Aisha, Raza, Shehzad, Shazad, Muhammad, Nasim, Sana, Javed, Muhammad Ahsan, Ali, Syed Saadat, Jafree, Mehmood, Nisar, Muhammad Imran, Daood, Muhammad Salman, Hussain, Altaf, Sarwar, Nadeem, Kamal, Ayeesha, Deloukas, Panos, Ishaq, Muhammad, Frossard, Philippe, and Danesh, John

Published
2009
Full Text
View/download PDF

32. EXTH-58. THERAPEUTIC HDAC INHIBITION IN HYPERMUTANT DIFFUSE INTRINSIC PONTINE GLIOMA

Author

Noll, Alyssa, primary, Biery, Matt, additional, Myers, Carrie, additional, Paine, Danyelle, additional, Zheng, Ye, additional, Girard, Emily, additional, Winter, Conrad, additional, Morris, Shelli, additional, Brusniak, Mi-Youn, additional, Gottardo, Raphael, additional, Mhyre, Andrew, additional, Foster, Jessica, additional, Dun, Matthew, additional, Murtaza, Muhammed, additional, Berens, Michael, additional, Olson, James, additional, and Vitanza, Nicholas, additional

Published
2021
Full Text
View/download PDF

34. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA

Author

Murtaza, Muhammed, Dawson, Sarah-Jane, Tsui, Dana W.Y., Gale, Davina, Forshew, Tim, Piskorz, Anna M., Parkinson, Christine, Chin, Suet-Feung, Kingsbury, Zoya, Wong, Alvin S.C., Marass, Francesco, Humphray, Sean, Hadfield, James, Bentley, David, Chin, Tan Min, Brenton, James D., Caldas, Carlos, and Rosenfeld, Nitzan

Subjects
Nucleotide sequencing -- Research -- Physiological aspects -- Genetic aspects, Antineoplastic agents -- Dosage and administration -- Research, DNA sequencing -- Research -- Physiological aspects -- Genetic aspects, Drug resistance -- Research -- Genetic aspects, Cancer -- Care and treatment, Blood plasma -- Physiological aspects -- Genetic aspects -- Research, Antimitotic agents -- Dosage and administration -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Cancers acquire resistance to systemic treatment as a result of clonal evolution and selection (1,2). Repeat biopsies to study genomic evolution as a result of therapy are difficult, invasive and [...]

Published
2013

37. Virus-free CRISPR knock-in of a chimeric antigen receptor into KLRC1generates potent GD2-specific natural killer cells

Author

Shankar, Keerthana, Zingler-Hoslet, Isabelle, Tabima, Diana M., Zima, Seth, Shi, Lei, Gimse, Kirstan, Forsberg, Matthew H., Katta, Varun, Davis, Sage Z., Maldonado, Daniel, Russell, Brittany E., Murtaza, Muhammed, Tsai, Shengdar Q., Ayuso, Jose M., Capitini, Christian M., and Saha, Krishanu

Abstract

Natural killer (NK) cells are an appealing off-the-shelf, allogeneic cellular therapy due to their cytotoxic profile. However, their activity against solid tumors remains suboptimal in part due to the upregulation of NK-inhibitory ligands, such as HLA-E, within the tumor microenvironment. Here, we utilize CRISPR-Cas9 to disrupt the KLRC1gene (encoding the HLA-E-binding NKG2A receptor) and perform non-viral insertion of a GD2-targeting chimeric antigen receptor (CAR) within NK cells isolated from human peripheral blood. Genome editing with CRISPR/Cas9 ribonucleoprotein complexes yields efficient genomic disruption of the KLRC1gene with 98% knockout efficiency and specific knock-in of the GD2 CAR transgene as high as 23%, with minimal off-target activity as shown by CHANGE-Seq, in-out PCR, amplicon sequencing and long read whole genome sequencing. KLRC1-GD2 CAR NK cells display high viability and proliferation, as well as precise cellular targeting and potency against GD2+human tumor cells. Notably, KLRC1-GD2 CAR NK cells overcome HLA-E-based inhibition in vitroagainst HLA-E-expressing, GD2+melanoma cells. Using a single-step, virus-free genome editing workflow, this study demonstrates the feasibility of precisely disrupting inhibitory signaling within NK cells via CRISPR/Cas9 while expressing a CAR to generate potent allogeneic cell therapies against HLA-E+solid tumors.

Published
2025
Full Text
View/download PDF

38. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis

Author

Weaver, Jamie MJ, Ross-Innes, Caryn S, Shannon, Nicholas, Lynch, Andy G, Forshew, Tim, Barbera, Mariagnese, Murtaza, Muhammed, Ong, Chin-Ann J, Lao-Sirieix, Pierre, Dunning, Mark J, Smith, Laura, Smith, Mike L, Anderson, Charlotte L, Carvalho, Benilton, O'Donovan, Maria, Underwood, Timothy J, May, Andrew P, Grehan, Nicola, Hardwick, Richard, Davies, Jim, Oloumi, Arusha, Aparicio, Sam, Caldas, Carlos, Eldridge, Matthew D, Edwards, Paul AW, Rosenfeld, Nitzan, Tavaré, Simon, Fitzgerald, Rebecca C, OCCAMS Consortium, Lynch, Andy [0000-0002-7876-7338], Dunning, Mark [0000-0002-8853-9435], Caldas, Carlos [0000-0003-3547-1489], Eldridge, Matthew [0000-0002-5799-8911], Edwards, Paul [0000-0002-4789-3374], Rosenfeld, Nitzan [0000-0002-2825-4788], Fitzgerald, Rebecca [0000-0002-3434-3568], and Apollo - University of Cambridge Repository

Subjects
Cancer genome sequencing, Adult, Male, Esophageal Neoplasms, Carcinogenesis, ICGC, Biology, Adenocarcinoma, medicine.disease_cause, Malignancy, Somatic evolution in cancer, Article, Barrett Esophagus, Genetics, medicine, Barrett’s esophagus, Humans, esophageal cancer, Barretts esophagus, Aged, Aged, 80 and over, whole genome sequencing, Mutation, Sequence Analysis, DNA, Middle Aged, medicine.disease, digestive system diseases, 3. Good health, Dysplasia, Cancer research, Female, Precancerous Conditions, Genome-Wide Association Study
Abstract

Cancer genome sequencing studies have identified numerous driver genes, but the relative timing of mutations in carcinogenesis remains unclear. The gradual progression from premalignant Barrett's esophagus to esophageal adenocarcinoma (EAC) provides an ideal model to study the ordering of somatic mutations. We identified recurrently mutated genes and assessed clonal structure using whole-genome sequencing and amplicon resequencing of 112 EACs. We next screened a cohort of 109 biopsies from 2 key transition points in the development of malignancy: benign metaplastic never-dysplastic Barrett's esophagus (NDBE; n=66) and high-grade dysplasia (HGD; n=43). Unexpectedly, the majority of recurrently mutated genes in EAC were also mutated in NDBE. Only TP53 and SMAD4 mutations occurred in a stage-specific manner, confined to HGD and EAC, respectively. Finally, we applied this knowledge to identify high-risk Barrett's esophagus in a new non-endoscopic test. In conclusion, mutations in EAC driver genes generally occur exceptionally early in disease development with profound implications for diagnostic and therapeutic strategies.

Published
2020
Full Text
View/download PDF

39. Analysis of fragment ends in plasma DNA from patients with cancer

Author

Budhraja, Karan K., primary, McDonald, Bradon R., additional, Stephens, Michelle D., additional, Contente-Cuomo, Tania, additional, Markus, Havell, additional, Farooq, Maria, additional, Favaro, Patricia F., additional, Connor, Sydney, additional, Byron, Sara A., additional, Egan, Jan B., additional, Ernst, Brenda, additional, McDaniel, Timothy K., additional, Sekulic, Aleksandar, additional, Tran, Nhan L., additional, Prados, Michael D., additional, Borad, Mitesh J., additional, Berens, Michael E., additional, Pockaj, Barbara A., additional, LoRusso, Patricia M., additional, Bryce, Alan, additional, Trent, Jeffrey M., additional, and Murtaza, Muhammed, additional

Published
2021
Full Text
View/download PDF

40. Horizons in Veterinary Precision Oncology: Fundamentals of Cancer Genomics and Applications of Liquid Biopsy for the Detection, Characterization, and Management of Cancer in Dogs

Author

Chibuk, Jason, primary, Flory, Andi, additional, Kruglyak, Kristina M., additional, Leibman, Nicole, additional, Nahama, Alexis, additional, Dharajiya, Nilesh, additional, van den Boom, Dirk, additional, Jensen, Taylor J., additional, Friedman, Jeffrey S., additional, Shen, M. Richard, additional, Clemente-Vicario, Francisco, additional, Chorny, Ilya, additional, Tynan, John A., additional, Lytle, Katherine M., additional, Holtvoigt, Lauren E., additional, Murtaza, Muhammed, additional, Diaz, Luis A., additional, Tsui, Dana W. Y., additional, and Grosu, Daniel S., additional

Published
2021
Full Text
View/download PDF

41. Analysis of recurrently protected genomic regions in cell-free DNA found in urine

Author

Markus, Havell, primary, Zhao, Jun, additional, Contente-Cuomo, Tania, additional, Stephens, Michelle D., additional, Raupach, Elizabeth, additional, Odenheimer-Bergman, Ahuva, additional, Connor, Sydney, additional, McDonald, Bradon R., additional, Moore, Bethine, additional, Hutchins, Elizabeth, additional, McGilvrey, Marissa, additional, de la Maza, Michelina C., additional, Van Keuren-Jensen, Kendall, additional, Pirrotte, Patrick, additional, Goel, Ajay, additional, Becerra, Carlos, additional, Von Hoff, Daniel D., additional, Celinski, Scott A., additional, Hingorani, Pooja, additional, and Murtaza, Muhammed, additional

Published
2021
Full Text
View/download PDF

42. Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer

Author

Dawson, Sarah-Jane, Tsui, Dana W.Y., Murtaza, Muhammed, Biggs, Heather, Rueda, Oscar M., Chin, Suet-Feung, Dunning, Mark J., Gale, Davina, Forshew, Tim, Mahler-Araujo, Betania, Rajan, Sabrina, Humphray, Sean, Becq, Jennifer, Halsall, David, Wallis, Matthew, Bentley, David, Caldas, Carlos, and Rosenfeld, Nitzan

Published
2013
Full Text
View/download PDF

43. Genomic landscapes of canine splenic angiosarcoma (hemangiosarcoma) contain extensive heterogeneity within and between patients

Author

Wong, Shukmei, primary, Ehrhart, EJ, additional, Stewart, Samuel, additional, Zismann, Victoria, additional, Cawley, Jacob, additional, Halperin, Rebecca, additional, Briones, Natalia, additional, Richter, Keith, additional, Sivaprakasam, Karthigayini, additional, Perdigones, Nieves, additional, Contente-Cuomo, Tania, additional, Facista, Salvatore, additional, Trent, Jeffrey M., additional, Murtaza, Muhammed, additional, Khanna, Chand, additional, and Hendricks, William P. D., additional

Published
2020
Full Text
View/download PDF

44. Primary glomus tumour of the pituitary gland: diagnostic challenges of a rare and potentially aggressive neoplasm

Author

Quah, Boon Leong, primary, Donofrio, Carmine Antonio, additional, La Rosa, Stefano, additional, Brouland, Jean-Philippe, additional, Cossu, Giulia, additional, Djoukhadar, Ibrahim, additional, Mayers, Helen, additional, Shenjere, Patrick, additional, Pereira, Marta, additional, Pathmanaban, Omar N., additional, Murtaza, Muhammed O., additional, Gattamaneni, Rao, additional, Roncaroli, Federico, additional, and Karabatsou, Konstantina, additional

Published
2020
Full Text
View/download PDF

47. Abstract PR14: Sub-nucleosomal fragmentation in urine cell-free DNA

Author

Markus, Havell, primary, Zhao, Jun, additional, Contente-Cuomo, Tania, additional, Raupach, Elizabeth, additional, Odenheimer-Bergman, Ahuva, additional, Connor, Sydney, additional, McDonald, Bradon, additional, Hutchins, Elizabeth, additional, McGilvrey, Marissa, additional, de la Maza, Michelina C., additional, Van Jensen, Kendall Van Keuren-Jensen, additional, Pirrotte, Patrick Pirrotte, additional, Goel, Ajay, additional, Becerra, Carlos, additional, Von Hoff, Daniel D., additional, Celinski, Scott, additional, Hingorani, Pooja, additional, and Murtaza, Muhammed, additional

Published
2020
Full Text
View/download PDF

48. Abstract A51: Personalized monitoring of treatment response using Targeted Digital Sequencing of circulating tumor DNA

Author

McDonald, Bradon R., primary, Contente-Cuomo, Tania, additional, Sammut, Stephen-John, additional, Stephens, Michelle D., additional, Odenheimer-Bergman, Ahuva, additional, Ernst, Brenda, additional, Perdigones, Nieves, additional, Chin, Suet-Feung, additional, Farooq, Maria, additional, Mejia, Rosa, additional, Cronin, Patricia A., additional, Anderson, Karen S., additional, Kosiorek, Heidi E., additional, Northfelt, Donald W., additional, McCullough, Ann E., additional, Patel, Bhavika K., additional, Weitzel, Jeffrey N., additional, Slavin, Thomas P., additional, Caldas, Carlos, additional, Pockaj, Barbara A., additional, and Murtaza, Muhammed, additional

Published
2020
Full Text
View/download PDF

49. Circulating tumor DNA as an early cancer detection tool

Author

Campos-Carrillo, Andrea, primary, Weitzel, Jeffrey N., additional, Sahoo, Prativa, additional, Rockne, Russell, additional, Mokhnatkin, Janet V., additional, Murtaza, Muhammed, additional, Gray, Stacy W., additional, Goetz, Laura, additional, Goel, Ajay, additional, Schork, Nicholas, additional, and Slavin, Thomas P., additional

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results