Subclonal reconstruction of tumors by using machine learning and population genetics

Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer
Hamzeh Kayhanian, William Cross, Suzanne E. M. van der Horst, Panagiotis Barmpoutis, Eszter Lakatos, Giulio Caravagna, Luis Zapata, Arne Van Hoeck, Sjors Middelkamp, Kevin Litchfield, Christopher Steele, William Waddingham, Dominic Patel, Salvatore Milite, Chen Jin, Ann-Marie Baker, Daniel C. Alexander, Khurum Khan, Daniel Hochhauser, Marco Novelli, Benjamin Werner, Ruben van Boxtel, Joris H. Hageman, Julian R. Buissant des Amorie, Josep Linares, Marjolijn J. L. Ligtenberg, Iris D. Nagtegaal, Miangela M. Laclé, Leon M. G. Moons, Lodewijk A. A. Brosens, Nischalan Pillay, Andrea Sottoriva, Trevor A. Graham, Manuel Rodriguez-Justo, Kai-Keen Shiu, Hugo J. G. Snippert, Marnix Jansen and Cross, W. 2024. Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer. Nature Genetics. 56, pp. 1420-1433. https://doi.org/10.1038/s41588-024-01777-9

Closing the loop – the role of pathologists in digital and computational pathology research
Tilman T. Rau, William Cross, Ricardo R. Lastra, Regina C‐L. Lo, Andres Matoso and C. Simon Herrington 2024. Closing the loop – the role of pathologists in digital and computational pathology research. The Journal of Pathology: Clinical Research. 10 (2) e12366. https://doi.org/10.1002/2056-4538.12366

Insights for precision oncology from the integration of genomic and clinical data of 13,880 tumors from the 100,000 Genomes Cancer Programme
Alona Sosinsky, John Ambrose, William Cross, Clare Turnbull, Shirley Henderson, Louise Jones, Angela Hamblin, Prabhu Arumugam, Georgia Chan, Daniel Chubb, Boris Noyvert, Jonathan Mitchell, Susan Walker, Katy Bowman, Dorota Pasko, Marianna Buongermino Pereira, Nadezda Volkova, Antonio Rueda-Martin, Daniel Perez-Gil, Javier Lopez, John Pullinger, Afshan Siddiq, Tala Zainy, Tasnim Choudhury, Olena Yavorska, Tom Fowler, David Bentley, Clare Kingsley, Sandra Hing, Zandra Deans, Augusto Rendon, Sue Hill, Mark Caulfield and Nirupa Murugaesu 2024. Insights for precision oncology from the integration of genomic and clinical data of 13,880 tumors from the 100,000 Genomes Cancer Programme. Nature Medicine. 30, pp. 279-289. https://doi.org/10.1038/s41591-023-02682-0

Germline MBD4 deficiency causes a multi-tumor predisposition syndrome
Claire Palles, Hannah D. West, Edward Chew, Sara Galavotti, Christoffer Flensburg, Judith E. Grolleman, Erik A.M. Jansen, Helen Curley, Laura Chegwidden, Edward H. Arbe-Barnes, Nicola Lander, Rebekah Truscott, Judith Pagan, Ashish Bajel, Kitty Sherwood, Lynn Martin, Huw Thomas, Demetra Georgiou, Florentia Fostira, Yael Goldberg, David J. Adams, Simone A.M. van der Biezen, Michael Christie, Mark Clendenning, Laura E. Thomas, Constantinos Deltas, Aleksandar J. Dimovski, Dagmara Dymerska, Jan Lubinski, Khalid Mahmood, Rachel S. van der Post, Mathijs Sanders, Jürgen Weitz, Jenny C. Taylor, Clare Turnbull, Lilian Vreede, Tom van Wezel, Celina Whalley, Claudia Arnedo-Pac, Giulio Caravagna, William Cross, Daniel Chubb, Anna Frangou, Andreas J. Gruber, Ben Kinnersley, Boris Noyvert, David Church, Trevor Graham, Richard Houlston, Nuria Lopez-Bigas and Andrea Sottoriva 2022. Germline MBD4 deficiency causes a multi-tumor predisposition syndrome. The American Journal of Human Genetics. 109 (5), pp. P953-960. https://doi.org/10.1016/j.ajhg.2022.03.018

Immunosuppressive niche engineering at the onset of human colorectal cancer
Chandler Gatenbee, Ann-Marie Baker, Ryan Schenck, Maximilian Strobl, Jeffrey West, Margarida P. Neves, Sara Yakub Hasan, Eszter Lakatos, Pierre Martinez, William C. H. Cross, Marnix Jansen, Manuel Rodriguez-Justo, Christopher Whelan, Andrea Sottoriva, Simon Leedham, Mark Robertson-Tessi, Trevor Graham and Alexander R.A. Anderson 2022. Immunosuppressive niche engineering at the onset of human colorectal cancer. Nature Communications . 13 1798. https://doi.org/10.1038/s41467-022-29027-8

Preprint: Mutation Rate Evolution Drives Immune Escape In Mismatch Repair-Deficient Cancer
Hamzeh Kayhanian, Panagiotis Barmpoutis, Eszter Lakatos, William Cross, Giulio Caravagna, Luis Zapata, Kevin Litchfield, Christopher Steele, William Waddingham, Dominic Patel, Salvatore Milite, Chen Jin, Ann-Marie Baker, Christopher Ross, Daniel Alexander, Khurum Khan, Daniel Hochhauser, Marco Novelli, Benjamin Werner, Naomi Guppy, Josep Linares, Marjolijn J.L. Ligtenberg, Iris D. Nagtegaal, Andrea Sottoriva, Trevor Graham, Nischalan Pillay, Manuel Rodriguez-Justo, Kai-Keen Shiu, Marnix Jansen and Genomics England Research Consortium 2022. Preprint: Mutation Rate Evolution Drives Immune Escape In Mismatch Repair-Deficient Cancer. biorxiv.org. https://doi.org/10.1101/2022.03.06.482973

A genetic model for central chondrosarcoma evolution correlates with patient outcome
William Cross, Iben Lyskjær, Tom Lesluyes, Steven Hargreaves, Anna-Christina Strobl, Christopher Davies, Sara Waise, Shadi Hames-Fathi, Dahmane Oukrif, Hongtao Ye, Fernanda Amary, Roberto Tirabosco, Craig Gerrand, Toby Baker, David Barnes, Christopher Steele, Ludmil Alexandrov, Gareth Bond, Paul Cool, Nischalan Pillay, Peter Van Loo and Adrienne M. Flanagan 2022. A genetic model for central chondrosarcoma evolution correlates with patient outcome. Genome Medicine. 14 99. https://doi.org/10.1186/s13073-022-01084-0

Preprint: Integrated quality control of allele-specific copy numbers, mutations and tumour purity from cancer whole genome sequencing assays
Jacob Househam, Riccardo Bergamin, Salvatore Milite, Nicola Calonaci, Alice Antonello, Marc J. Williams, William C.H. Cross and Giulio Caravagna 2022. Preprint: Integrated quality control of allele-specific copy numbers, mutations and tumour purity from cancer whole genome sequencing assays. biorxiv.org. https://doi.org/10.1101/2021.02.13.429885

Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations
Iben Lyskjær, Christopher Davies, Anna‐Christina Strobl, Joanna Hindley, Steven James, Radhesh K. Lalam, William Cross, Geoff Hide, Kenneth S. Rankin, Lee Jeys, Roberto Tirabosco, Jonathan Stevenson, Paul O’Donnell, Paul Cool, Adrienne M. Flanagan and Genomics England Research Consortium 2021. Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations. Molecular Oncology. 15 (12), pp. 3679-3690. https://doi.org/10.1002/1878-0261.13102

The early evolutionary landscape of osteosarcoma provides clues for targeted treatment strategies
Michal Kovac, Baptiste Ameline, Sebastian Ribi, Monika Kovacova, William Cross, Maxim Barenboim, Olaf Witt, Stefan Bielack, Andreas Krieg, Wolfgang Hartmann, Michaela Nathrath and Daniel Baumhoer 2021. The early evolutionary landscape of osteosarcoma provides clues for targeted treatment strategies. The Journal of Pathology. 254 (5), pp. 556-566. https://doi.org/10.1002/path.5699

Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns
Yannik Bollen, Ellen Stelloo, Petra van Leenen, Myrna van den Bos, Bas Ponsioen, Bingxin Lu, Markus J. van Roosmalen, Ana C.F. Bolhaqueiro, Christopher Kimberley, Maximilian Mossner, William C.H. Cross, Nicolle Besselink, Bastiaan Van der Roest, Sander Boymans, Koen C. Oost, Sippe G. de Vries, Holger Rehmann, Edwin Cuppen, Susanne M.A. Lens, Geert Kops, Wigard P. Kloosterman, Leon Terstappen, Chris Barnes, Andrea Sottoriva, Trevor Graham and Hugo Snippert 2021. Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns. Nature Genetics. 53, pp. 1187-1195. https://doi.org/10.1038/s41588-021-00891-2

Preprint: A Genetic Model for Central Chondrosarcoma Evolution Correlates with Patient Outcome
William Cross, Iben Lyskjær, Tom Lesluyes, Steven Hargreaves, Anna-Christina Strobl, Christopher Davies, Sara Waise, Shadi Hames, Dahmane Oukrif, Hongtao Ye, Fernanda Amary, Roberto Tirabosco, Toby Baker, David Barnes, Christopher Steele, Ludmil Alexandrov, Gareth Bond, Paul Cool, Nischalan Pillay, Peter Van Loo and Adrienne M. Flanagan 2021. Preprint: A Genetic Model for Central Chondrosarcoma Evolution Correlates with Patient Outcome. medRxiv. https://doi.org/10.1101/2021.11.02.21265785

Measuring single cell divisions in human tissues from multi-region sequencing data
Benjamin Werner, Jack Case, Marc Williams, Ketevan Chkhaidze, Daniel Temko, Javier Fernández-Mateos, George David Cresswell, Daniel Nichol, William Cross, Inmaculada Spiteri, Weini Huang, Tomlinson, I., Chris Barnes, Trevor Graham and Andrea Sottoriva 2020. Measuring single cell divisions in human tissues from multi-region sequencing data. Nature Communications . 11 1035. https://doi.org/10.1038/s41467-020-14844-6

Sarcoma and the 100,000 Genomes Project: our experience and changes to practice
Sophie C Prendergast, Anna‐Christina Strobl, William Cross, Nischalan Pillay, Sandra J Strauss, Hongtao Ye, Daniel Lindsay, Roberto Tirabosco, Jane Chalker, Shazia S Mahamdallie, Alona Sosinsky, Adrienne M Flanagan, Fernanda Amary, RNOH Pathology Laboratory and Biobank Team and Genomics England Research Consortium 2020. Sarcoma and the 100,000 Genomes Project: our experience and changes to practice. The Journal of Pathology: Clinical Research. 6 (4), pp. 297-307. https://doi.org/10.1002/cjp2.174

Stabilising selection causes grossly altered but stable karyotypes in metastatic colorectal cancer
William Cross, Maximilian Mossner, Salpie Nowinski, George Cresswell, Abhirup Banerjee, Marc Williams, Laura Gay, Ann-Marie Baker, Christopher Kimberley, Hayley Davis, Pierre Martinez, Maria Traki, Viola Walther, Kane Smith, Giulio Caravagna, Sasikumar Amarasingam, George Elia, Alison Berner, Ryan Changho Choi, Pradeep Ramagiri, Ritika Chauhan, Nik Matthews, Jamie Murphy, Anthony Antoniou, Susan Clark, Jo-Anne Chin Aleong, Enric Domingo, Inmaculada Spiteri, Stuart AC McDonald, Darryl Shibata, Miangela M Lacle, Lai Mun Wang, Morgan Moorghen, Ian PM Tomlinson, Marco Novelli, Marnix Jansen, Alan Watson, Nicholas A Wright, John Bridgewater, Manuel Rodriguez-Justo, Hemant Kocher, Simon J Leedham, Andrea Sottoriva and Trevor A Graham 2020. Stabilising selection causes grossly altered but stable karyotypes in metastatic colorectal cancer. biorxiv.org. https://doi.org/10.1101/2020.03.26.007138

Convergent Evolution of Copy Number Alterations in Multi-Centric Hepatocellular Carcinoma
Carolin Lackner, Luca Quagliata, William Cross, Sebastian Ribi, Karl Heinimann, Viola Paradiso, Cristina Quintavalle, Monika Kovacova, Daniel Baumhoer, Salvatore Piscuoglio, Luigi Terracciano and Michal Kovac 2019. Convergent Evolution of Copy Number Alterations in Multi-Centric Hepatocellular Carcinoma. Scientific Reports. 9 4611. https://doi.org/10.1038/s41598-019-40843-9

Evolutionary history of human colitis-associated colorectal cancer
Ann-Marie Baker, William Cross, Kit Curtius, Ibrahim Al Bakir, Chang-Ho Ryan Choi, Hayley Louise Davis, Daniel Temko, Sujata Biswas, Pierre Martinez, Marc J. Williams, James O. Lindsay, Roger Feakins, Roser Vega, Stephen J. Hayes, Tomlinson, I., Stuart A.C. McDonald, Morgan Moorghen, Andrew Silver, James E. East, Nicholas A. Wright, Lai Mun Wang, Manuel Rodriguez-Justo, Marnix Jansen, Ailsa L. Hart, Simon J. Leedham and Trevor Graham 2019. Evolutionary history of human colitis-associated colorectal cancer. Gut. 68, pp. 985-995. https://doi.org/10.1136/gutjnl-2018-316191

Preprint: Niche engineering drives early passage through an immune bottleneck in progression to colorectal cancer
Chandler D. Gatenbee, Ann-Marie Baker, Ryan O. Schenck, Margarida Neves, Sara Yakub Hasan, Pierre Martinez, William C.H. Cross, Marnix Jansen, Manuel Rodriguez-Justo, Andrea Sottoriva, Simon Leedham, Mark Robertson-Tessi, Trevor A. Graham and Alexander Anderson 2019. Preprint: Niche engineering drives early passage through an immune bottleneck in progression to colorectal cancer. biorxiv.org. https://doi.org/10.1101/623959

Preprint: Model-based tumor subclonal reconstruction
Giulio Caravagna, Timon Heide, Marc Williams, Luis Zapata, Daniel Nichol, Ketevan Chkhaidze, William Cross, George D. Cresswell, Benjamin Werner, Ahmet Acar, Chris P. Barnes, Guido Sanguinetti, Trevor A. Graham and Andrea Sottoriva 2019. Preprint: Model-based tumor subclonal reconstruction. biorxiv.org. https://doi.org/10.1101/586560

Preprint: Evolutionary dynamics of neoantigens in growing tumours
Eszter Lakatos, Marc J. Williams, Ryan O. Schenck, William C. H. Cross, Jacob Househam, Benjamin Werner, Chandler Gatenbee, Mark Robertson-Tessi, Chris P. Barnes, Alexander R. A. Anderson, Andrea Sottoriva and Trevor A. Graham 2019. Preprint: Evolutionary dynamics of neoantigens in growing tumours. biorxiv.org. https://doi.org/10.1101/536433

The evolutionary landscape of colorectal tumorigenesis
William Cross, Michal Kovac, Ville Mustonen, Daniel Temko, Hayley Davis, Ann-Marie Baker, Sujata Biswas, Roland Arnold, Laura Chegwidden, Chandler Gatenbee, Alexander R.A. Anderson, Viktor Koelzer, Pierre Martinez, Xiaowei Jiang, Enric Domingo, Dan J. Woodcock, Yun Feng, Monika Kovacova, Tim Maughan, Richard Adams, Simon Bach, Andrew Beggs, Louise Brown, Francesca Buffa, Jean-Baptiste Cazier, Enric Domingo, Andrew Blake, Che-Hsi Wu, Ekaterina Chatzpili, Susan Richman, Philip Dunne, Paul Harkin, Geoff Higgins, Jim Hill, Chris Holmes, Denis Horgan, Rick Kaplan, Richard Kennedy, Mark Lawler, Simon Leedham, Tim Maughan, Ultan McDermott, Gillies McKenna, Gary Middleton, Dion Morton, Graeme Murray, Phil Quirke, Manuel Salto-Tellez, Les Samuel, Anna Schuh and David Sebag-Montefiore 2018. The evolutionary landscape of colorectal tumorigenesis. Nature Ecology & Evolution. 2, pp. 1661-1672. https://doi.org/10.1038/s41559-018-0642-z

New paradigms in clonal evolution: punctuated equilibrium in cancer
Cross, W., Graham, T.M. and Wright, N.A. 2016. New paradigms in clonal evolution: punctuated equilibrium in cancer. The Journal of Pathology. 240 (2), pp. 126-136. https://doi.org/10.1002/path.4757

Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy
Findlay, J.M., Castro-Giner, F., Makino, S., Rayner, E., Kartsonaki, C., Cross, W., Kovac, M., Ulahannan, D., Palles, C., Gillies, R.S., MacGregor, T.P. and Church, D. 2016. Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy. Nature Communications . 7 11111. https://doi.org/10.1038/ncomms11111

Variation in tau isoform expression in different brain regions and disease states
Majounie, E., Cross, W., Newsway, V., Dillman, A., Vandrovcova, J., Morris, C.M., Nalls, M.A., Ferrucci, E., Owen, M.J., O'Donovan, M.C., Cookson, M.R., Singleton, A.B., de Silva, R. and Morris, H.R. 2013. Variation in tau isoform expression in different brain regions and disease states. Neurobiology of Aging. 34 (7), pp. 1922.e7-1922.e12. https://doi.org/10.1016/j.neurobiolaging.2013.01.017

The effect of age and the H1c MAPT haplotype on MAPT expression in human brain
Hayesmoore, J.B.G., Bray, N.J., Cross, W., Owen, M.J., O’Donovan, M.C. and Morris, H.R. 2009. The effect of age and the H1c MAPT haplotype on MAPT expression in human brain. Neurobiology of Aging. 30 (10), pp. 1652-1656. https://doi.org/10.1016/j.neurobiolaging.2007.12.017

Case control analysis of repeat expansion size in ataxia
Majounie, E., Wardle, M., Muzaimi, M., Cross, W., Robertson, N.P., Williams, N.M. and Morris, H.R. 2007. Case control analysis of repeat expansion size in ataxia. Neuroscience Letters. 429 (1), pp. 28-32. https://doi.org/10.1016/j.neulet.2007.09.055