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Pancreatic Neoplasms: HELP
Articles by Peter J. Campbell
Based on 6 articles published since 2009
(Why 6 articles?)
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Between 2009 and 2019, Peter J. Campbell wrote the following 6 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. 2017

Davies, Helen / Glodzik, Dominik / Morganella, Sandro / Yates, Lucy R / Staaf, Johan / Zou, Xueqing / Ramakrishna, Manasa / Martin, Sancha / Boyault, Sandrine / Sieuwerts, Anieta M / Simpson, Peter T / King, Tari A / Raine, Keiran / Eyfjord, Jorunn E / Kong, Gu / Borg, Åke / Birney, Ewan / Stunnenberg, Hendrik G / van de Vijver, Marc J / Børresen-Dale, Anne-Lise / Martens, John W M / Span, Paul N / Lakhani, Sunil R / Vincent-Salomon, Anne / Sotiriou, Christos / Tutt, Andrew / Thompson, Alastair M / Van Laere, Steven / Richardson, Andrea L / Viari, Alain / Campbell, Peter J / Stratton, Michael R / Nik-Zainal, Serena. ·Wellcome Trust Sanger Institute, Hinxton, UK. · Guy's and St Thomas' NHS Trust, London, UK. · Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden. · Oncology, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Little Chesterford, UK. · Translational Research Lab Department, Centre Léon Bérard, Lyon, France. · Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics, Erasmus University Medical Center, Rotterdam, the Netherlands. · Centre for Clinical Research and School of Medicine, The University of Queensland, Brisbane, Queensland, Australia. · Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Cancer Research Laboratory, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. · Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea. · European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, UK. · Department of Molecular Biology, Faculties of Science and Medicine, Radboud University, Nijmegen, the Netherlands. · Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands. · Department of Cancer Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. · K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo, Norway. · Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands. · Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. · Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. · Department of Pathology, Institut Curie, Paris, France. · INSERM U934, Institut Curie, Paris, France. · Breast Cancer Translational Research Laboratory, Université Libre de Bruxelles, Institut Jules Bordet, Brussels, Belgium. · Breast Cancer Now Research Unit, King's College, London, UK. · Breast Cancer Now Toby Robin's Research Centre, Institute of Cancer Research, London, UK. · Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Translational Cancer Research Unit, Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. · HistoGeneX, Wilrijk, Belgium. · Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Dana-Farber Cancer Institute, Boston, Massachusetts, USA. · Equipe Erable, INRIA Grenoble-Rhône-Alpes, Montbonnot-Saint Martin, France. · Synergie Lyon Cancer, Centre Léon Bérard, Lyon, France. · East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. ·Nat Med · Pubmed #28288110.

ABSTRACT: Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (∼1-5%) who could have selective therapeutic sensitivity to PARP inhibition.

2 Article A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns. 2016

Notta, Faiyaz / Chan-Seng-Yue, Michelle / Lemire, Mathieu / Li, Yilong / Wilson, Gavin W / Connor, Ashton A / Denroche, Robert E / Liang, Sheng-Ben / Brown, Andrew M K / Kim, Jaeseung C / Wang, Tao / Simpson, Jared T / Beck, Timothy / Borgida, Ayelet / Buchner, Nicholas / Chadwick, Dianne / Hafezi-Bakhtiari, Sara / Dick, John E / Heisler, Lawrence / Hollingsworth, Michael A / Ibrahimov, Emin / Jang, Gun Ho / Johns, Jeremy / Jorgensen, Lars G T / Law, Calvin / Ludkovski, Olga / Lungu, Ilinca / Ng, Karen / Pasternack, Danielle / Petersen, Gloria M / Shlush, Liran I / Timms, Lee / Tsao, Ming-Sound / Wilson, Julie M / Yung, Christina K / Zogopoulos, George / Bartlett, John M S / Alexandrov, Ludmil B / Real, Francisco X / Cleary, Sean P / Roehrl, Michael H / McPherson, John D / Stein, Lincoln D / Hudson, Thomas J / Campbell, Peter J / Gallinger, Steven. ·Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada. · Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. · UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, Ontario M5G 2C4, Canada. · Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada. · Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. · Department of Computer Science, University of Toronto, Toronto, Ontario M5S 3G4, Canada. · Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, Nebraska 68198, USA. · Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. · Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario M5G 2M9, Canada. · Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, Ontario M4N 3M5, Canada. · Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA. · Research Institute of the McGill University Health Centre, Montreal, Québec, Canada, H3H 2L9. · Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico, USA, 87545. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. · Department of Surgery, University Health Network, Toronto, Ontario M5G 2C4, Canada. · Department of Haematology, University of Cambridge, Cambridge CB2 0XY, UK. ·Nature · Pubmed #27732578.

ABSTRACT: Pancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours.

3 Article Signatures of mutational processes in human cancer. 2013

Alexandrov, Ludmil B / Nik-Zainal, Serena / Wedge, David C / Aparicio, Samuel A J R / 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 T W / 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 N J / Valdés-Mas, Rafael / van Buuren, Marit M / van 't Veer, Laura / Vincent-Salomon, Anne / Waddell, Nicola / Yates, Lucy R / Anonymous5950766 / Anonymous5960766 / Anonymous5970766 / Anonymous5980766 / 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. ·Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK. ·Nature · Pubmed #23945592.

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.

4 Article Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes. 2012

McBride, David J / Etemadmoghadam, Dariush / Cooke, Susanna L / Alsop, Kathryn / George, Joshy / Butler, Adam / Cho, Juok / Galappaththige, Danushka / Greenman, Chris / Howarth, Karen D / Lau, King W / Ng, Charlotte K / Raine, Keiran / Teague, Jon / Wedge, David C / Cancer Study Group, Australian Ovarian / Caubit, Xavier / Stratton, Michael R / Brenton, James D / Campbell, Peter J / Futreal, P Andrew / Bowtell, David Dl. ·Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK. david.bowtell@petermac.org ·J Pathol · Pubmed #22514011.

ABSTRACT: The application of paired-end next generation sequencing approaches has made it possible to systematically characterize rearrangements of the cancer genome to base-pair level. Utilizing this approach, we report the first detailed analysis of ovarian cancer rearrangements, comparing high-grade serous and clear cell cancers, and these histotypes with other solid cancers. Somatic rearrangements were systematically characterized in eight high-grade serous and five clear cell ovarian cancer genomes and we report here the identification of > 600 somatic rearrangements. Recurrent rearrangements of the transcriptional regulator gene, TSHZ3, were found in three of eight serous cases. Comparison to breast, pancreatic and prostate cancer genomes revealed that a subset of ovarian cancers share a marked tandem duplication phenotype with triple-negative breast cancers. The tandem duplication phenotype was not linked to BRCA1/2 mutation, suggesting that other common mechanisms or carcinogenic exposures are operative. High-grade serous cancers arising in women with germline BRCA1 or BRCA2 mutation showed a high frequency of small chromosomal deletions. These findings indicate that BRCA1/2 germline mutation may contribute to widespread structural change and that other undefined mechanism(s), which are potentially shared with triple-negative breast cancer, promote tandem chromosomal duplications that sculpt the ovarian cancer genome.

5 Article Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. 2011

Varela, Ignacio / Tarpey, Patrick / Raine, Keiran / Huang, Dachuan / Ong, Choon Kiat / Stephens, Philip / Davies, Helen / Jones, David / Lin, Meng-Lay / Teague, Jon / Bignell, Graham / Butler, Adam / Cho, Juok / Dalgliesh, Gillian L / Galappaththige, Danushka / Greenman, Chris / Hardy, Claire / Jia, Mingming / Latimer, Calli / Lau, King Wai / Marshall, John / McLaren, Stuart / Menzies, Andrew / Mudie, Laura / Stebbings, Lucy / Largaespada, David A / Wessels, L F A / Richard, Stephane / Kahnoski, Richard J / Anema, John / Tuveson, David A / Perez-Mancera, Pedro A / Mustonen, Ville / Fischer, Andrej / Adams, David J / Rust, Alistair / Chan-on, Waraporn / Subimerb, Chutima / Dykema, Karl / Furge, Kyle / Campbell, Peter J / Teh, Bin Tean / Stratton, Michael R / Futreal, P Andrew. ·Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. ·Nature · Pubmed #21248752.

ABSTRACT: The genetics of renal cancer is dominated by inactivation of the VHL tumour suppressor gene in clear cell carcinoma (ccRCC), the commonest histological subtype. A recent large-scale screen of ∼3,500 genes by PCR-based exon re-sequencing identified several new cancer genes in ccRCC including UTX (also known as KDM6A), JARID1C (also known as KDM5C) and SETD2 (ref. 2). These genes encode enzymes that demethylate (UTX, JARID1C) or methylate (SETD2) key lysine residues of histone H3. Modification of the methylation state of these lysine residues of histone H3 regulates chromatin structure and is implicated in transcriptional control. However, together these mutations are present in fewer than 15% of ccRCC, suggesting the existence of additional, currently unidentified cancer genes. Here, we have sequenced the protein coding exome in a series of primary ccRCC and report the identification of the SWI/SNF chromatin remodelling complex gene PBRM1 (ref. 4) as a second major ccRCC cancer gene, with truncating mutations in 41% (92/227) of cases. These data further elucidate the somatic genetic architecture of ccRCC and emphasize the marked contribution of aberrant chromatin biology.

6 Article The patterns and dynamics of genomic instability in metastatic pancreatic cancer. 2010

Campbell, Peter J / Yachida, Shinichi / Mudie, Laura J / Stephens, Philip J / Pleasance, Erin D / Stebbings, Lucy A / Morsberger, Laura A / Latimer, Calli / McLaren, Stuart / Lin, Meng-Lay / McBride, David J / Varela, Ignacio / Nik-Zainal, Serena A / Leroy, Catherine / Jia, Mingming / Menzies, Andrew / Butler, Adam P / Teague, Jon W / Griffin, Constance A / Burton, John / Swerdlow, Harold / Quail, Michael A / Stratton, Michael R / Iacobuzio-Donahue, Christine / Futreal, P Andrew. ·Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. ·Nature · Pubmed #20981101.

ABSTRACT: Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97-98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations, but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours, including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites, and how the tumour disseminates. Here we harness advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2-M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection.