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Your search keyword '"Aparicio, Samuel AJR"' showing total 9 results
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9 results on '"Aparicio, Samuel AJR"'

1. Mutational processes molding the genomes of 21 breast cancers

Author

Nik-Zainal, Serena, Alexandrov, Ludmil B, Wedge, David C, Van Loo, Peter, Greenman, Christopher D, Raine, Keiran, Jones, David, Hinton, Jonathan, Marshall, John, Stebbings, Lucy A, Menzies, Andrew, Martin, Sancha, Leung, Kenric, Chen, Lina, Leroy, Catherine, Ramakrishna, Manasa, Rance, Richard, Lau, King Wai, Mudie, Laura J, Varela, Ignacio, McBride, David J, Bignell, Graham R, Cooke, Susanna L, Shlien, Adam, Gamble, John, Whitmore, Ian, Maddison, Mark, Tarpey, Patrick S, Davies, Helen R, Papaemmanuil, Elli, Stephens, Philip J, McLaren, Stuart, Butler, Adam P, Teague, Jon W, Jönsson, Göran, Garber, Judy E, Silver, Daniel, Miron, Penelope, Fatima, Aquila, Boyault, Sandrine, Langerød, Anita, Tutt, Andrew, Martens, John WM, Aparicio, Samuel AJR, Borg, Åke, Salomon, Anne Vincent, Thomas, Gilles, Børresen-Dale, Anne-Lise, Richardson, Andrea L, Neuberger, Michael S, Futreal, P Andrew, Campbell, Peter J, Stratton, Michael R, Breast Cancer Working Group of the International Cancer Genome Consortium, Nik-Zainal Abidin, Serena [0000-0001-5054-1727], and Apollo - University of Cambridge Repository

Subjects
BRCA2 Protein, APOBEC-1 Deaminase, Cytidine Deaminase, DNA Mutational Analysis, Mutation, Genes, BRCA1, High-Throughput Nucleotide Sequencing, Humans, Breast Neoplasms, Female, Genome-Wide Association Study
Abstract

All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis," was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed.

Published
2020
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2. The life history of 21 breast cancers

Author

Nik-Zainal, Serena, Van Loo, Peter, Wedge, David C, Alexandrov, Ludmil B, Greenman, Christopher D, Lau, King Wai, Raine, Keiran, Jones, David, Marshall, John, Ramakrishna, Manasa, Shlien, Adam, Cooke, Susanna L, Hinton, Jonathan, Menzies, Andrew, Stebbings, Lucy A, Leroy, Catherine, Jia, Mingming, Rance, Richard, Mudie, Laura J, Gamble, Stephen J, Stephens, Philip J, McLaren, Stuart, Tarpey, Patrick S, Papaemmanuil, Elli, Davies, Helen R, Varela, Ignacio, McBride, David J, Bignell, Graham R, Leung, Kenric, Butler, Adam P, Teague, Jon W, Martin, Sancha, Jönsson, Goran, Mariani, Odette, Boyault, Sandrine, Miron, Penelope, Fatima, Aquila, Langerød, Anita, Aparicio, Samuel AJR, Tutt, Andrew, Sieuwerts, Anieta M, Borg, Åke, Thomas, Gilles, Salomon, Anne Vincent, Richardson, Andrea L, Børresen-Dale, Anne-Lise, Futreal, P Andrew, Stratton, Michael R, Campbell, Peter J, Breast Cancer Working Group of the International Cancer Genome Consortium, Nik-Zainal Abidin, Serena [0000-0001-5054-1727], and Apollo - University of Cambridge Repository

Subjects
Chromosome Aberrations, Clonal Evolution, Cell Transformation, Neoplastic, Mutation, Humans, Point Mutation, Breast Neoplasms, Female, Algorithms
Abstract

Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis.

Published
2020
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3. Signatures of mutational processes in human cancer

Author

Alexandrov, Ludmil B, Nik-Zainal, Serena, Wedge, David C, Aparicio, Samuel AJR, Behjati, Sam, Biankin, Andrew V, Bignell, Graham R, Bolli, Niccolò, Borg, Ake, Børresen-Dale, Anne-Lise, Boyault, Sandrine, Burkhardt, Birgit, Butler, Adam P, Caldas, Carlos, Davies, Helen R, Desmedt, Christine, Eils, Roland, Eyfjörd, Jórunn Erla, Foekens, John A, Greaves, Mel, Hosoda, Fumie, Hutter, Barbara, Ilicic, Tomislav, Imbeaud, Sandrine, Imielinski, Marcin, Jäger, Natalie, Jones, David TW, Jones, David, Knappskog, Stian, Kool, Marcel, Lakhani, Sunil R, López-Otín, Carlos, Martin, Sancha, Munshi, Nikhil C, Nakamura, Hiromi, Northcott, Paul A, Pajic, Marina, Papaemmanuil, Elli, Paradiso, Angelo, Pearson, John V, Puente, Xose S, Raine, Keiran, Ramakrishna, Manasa, Richardson, Andrea L, Richter, Julia, Rosenstiel, Philip, Schlesner, Matthias, Schumacher, Ton N, Span, Paul N, Teague, Jon W, Totoki, Yasushi, Tutt, Andrew NJ, Valdés-Mas, Rafael, van Buuren, Marit M, van 't Veer, Laura, Vincent-Salomon, Anne, Waddell, Nicola, Yates, Lucy R, Australian Pancreatic Cancer Genome Initiative, ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, ICGC PedBrain, Zucman-Rossi, Jessica, Futreal, P Andrew, McDermott, Ultan, Lichter, Peter, Meyerson, Matthew, Grimmond, Sean M, Siebert, Reiner, Campo, Elías, Shibata, Tatsuhiro, Pfister, Stefan M, Campbell, Peter J, Stratton, Michael R, Nik-Zainal Abidin, Serena [0000-0001-5054-1727], Caldas, Carlos [0000-0003-3547-1489], and Apollo - University of Cambridge Repository

Subjects
Aging, Models, Genetic, Transcription, Genetic, DNA Mutational Analysis, Reproducibility of Results, DNA, Mutagenesis, Insertional, Cell Transformation, Neoplastic, Mutagenesis, Organ Specificity, Cytidine Deaminase, Neoplasms, Mutation, Humans, Algorithms, Mutagens, Sequence Deletion
Abstract

All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.

Published
2013

7. Does massively parallel transcriptome analysis signify the end of cancer histopathology as we know it?

Author

Aparicio, Samuel AJR, Caldas, Carlos, and Ponder, Bruce

Subjects
Expressed Sequence Tags, Gene Expression Regulation, Neoplastic, Gene Expression Profiling, Biomarkers, Tumor, Humans, Breast Neoplasms, Minireview, RNA, Neoplasm, Neoplasm Staging, Oligonucleotide Array Sequence Analysis
Abstract

Transcriptional analysis of all the genes expressed by breast tumors has provided the first steps towards defining a molecular signature for the disease, and might ultimately make conventional diagnostic techniques obsolete.

Published
2000

8. Does massively parallel DNA resequencing signify the end of histopathology as we know it?

Author

Aparicio, Samuel AJR and Huntsman, David G

Abstract

Next-generation DNA sequencing devices have revolutionized cancer genomics by bringing whole genome resequencing of patients' tumours within practical and economic reach. We present an overview of the techniques involved and review early results from the resequencing of cancer genomes. The possible impacts of whole-genome and trancriptome resequencing in clinical cancer research and the practice of pathology are discussed. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2010
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9. Signatures of mutational processes in human cancer

Author

Alexandrov, Ludmil B, Nik-Zainal, Serena, Wedge, David C, Aparicio, Samuel AJR, Behjati, Sam, Biankin, Andrew V, Bignell, Graham R, Bolli, Niccolò, Borg, Ake, Børresen-Dale, Anne-Lise, Boyault, Sandrine, Burkhardt, Birgit, Butler, Adam P, Caldas, Carlos, Davies, Helen R, Desmedt, Christine, Eils, Roland, Eyfjörd, Jórunn Erla, Foekens, John A, Greaves, Mel, Hosoda, Fumie, Hutter, Barbara, Ilicic, Tomislav, Imbeaud, Sandrine, Imielinski, Marcin, Jäger, Natalie, Jones, David TW, Jones, David, Knappskog, Stian, Kool, Marcel, Lakhani, Sunil R, López-Otín, Carlos, Martin, Sancha, Munshi, Nikhil C, Nakamura, Hiromi, Northcott, Paul A, Pajic, Marina, Papaemmanuil, Elli, Paradiso, Angelo, Pearson, John V, Puente, Xose S, Raine, Keiran, Ramakrishna, Manasa, Richardson, Andrea L, Richter, Julia, Rosenstiel, Philip, Schlesner, Matthias, Schumacher, Ton N, Span, Paul N, Teague, Jon W, Totoki, Yasushi, Tutt, Andrew NJ, Valdés-Mas, Rafael, Van Buuren, Marit M, Van 'T Veer, Laura, Vincent-Salomon, Anne, Waddell, Nicola, Yates, Lucy R, Australian Pancreatic Cancer Genome Initiative, ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, ICGC PedBrain, Zucman-Rossi, Jessica, Futreal, P Andrew, McDermott, Ultan, Lichter, Peter, Meyerson, Matthew, Grimmond, Sean M, Siebert, Reiner, Campo, Elías, Shibata, Tatsuhiro, Pfister, Stefan M, Campbell, Peter J, and Stratton, Michael R

Subjects
Aging, Models, Genetic, Transcription, Genetic, DNA Mutational Analysis, Reproducibility of Results, DNA, 3. Good health, Mutagenesis, Insertional, Cell Transformation, Neoplastic, Mutagenesis, Organ Specificity, Cytidine Deaminase, Neoplasms, Mutation, Humans, Algorithms, Mutagens, Sequence Deletion
Abstract

All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.

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