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Allele-informed copy number evaluation of plasma DNA samples from metastatic prostate cancer patients: the PCF_SELECT consortium assay

2022; Oxford University Press; Volume: 4; Issue: 2 Linguagem: Inglês

10.1093/narcan/zcac016

2632-8674

Francesco Orlando, Alessandro Romanel, Blanca Trujillo, Michael Sigouros, Daniel Wetterskog, Orsetta Quaini, Gianmarco Leone, Jenny Xiang, Anna Wingate, Scott T. Tagawa, Anuradha Jayaram, Mark Linch, Charles Swanton, Mariam Jamal‐Hanjani, Chris Abbosh, Simone Zaccaria, Sonya Hessey, Kai‐Keen Shiu, John Bridgewater, Daniel Hochhauser, Martin Förster, SM Lee, Tanya Ahmad, Dionysis Papadatos-Pastos, Sam M. Janes, Peter Van Loo, Katey S.S. Enfield, Nicholas McGranahan, Ariana Huebner, Sergio A. Quezada, Stephan Beck, Peter J. Parker, Tariq Enver, Robert E. Hynds, Krijn K. Dijkstra, David R. Pearce, Mary Falzon, Ian Proctor, Ron Sinclair, Chi-wah Lok, Zoe Rhodes, David Moore, Teresa Marafioti, Miriam Mitchison, Peter Ellery, Monica Sivakumar, Mark Linch, Sebastian Brandner, Andrew Rowan, Crispin T. Hiley, Selvaraju Veeriah, Heather Shaw, G. Attard, Cristina Naceur‐Lombardelli, Antonia Toncheva, Paulina Prymas, Tom Watkins, C. Donovan Bailey, Carlos Martínez‐Ruiz, Kevin Litchfield, Maise Al-Bakir, Nnenna Kanu, Sophia Ward, Emilia L. Lim, James L. Reading, Benny Chain, Blanca Trujillo Alba, Tom Watkins, Melek Akay, Adrienne M. Flanagan, Dhruva Biswas, Oriol Pich, Michelle Dietzen, Clare Puttick, Emma Colliver, Alastair Magness, Mihaela Angelova, James R. Black, Olivia Lucas, William Hill, Wing-Kin Liu, Alexander M. Frankell, Neil Magno, Foteini Athanasopoulou, Gareth A. Wilson, Rachel Rosenthal, Roberto Salgado, Claudia Lee, Kristiana Grigoriadis, Othman Al‐Sawaf, Takahiro Karasaki, Abigail Bunkum, Imran Noorani, Sarah Benafif, Vittorio Barbè, Supreet Kaur Bola, Osvaldas Vainauskas, Anna Wingate, Daniel Wetterskog, Mahedi Hasan, Stefano Lise, Gianmarco Leone, Anuradha Jayaram, Constantine Alifrangis, Ursula McGovern, Kerstin Thol, Samuel Gamble, Seng Kuong Anakin Ung, Teerapon Sahwangarrom, Claudia Peinador Marin, Sophia Wong, Piotr Pawlik, Faye Gishen, Adrian Tookman, Paddy Stone, Caroline Stirling, Samra Turajlic, James Larkin, Lisa Pickering, Andrew Furness, Kate Young, Will Drake, Kim Edmonds, Nikki Hunter, Mary Mangwende, Karla Pearce, Lauren Grostate, Lewis Au, Lavinia Spain, Scott Shepherd, Haixi Yan, Benjamin Shum, Zayd Tippu, Brian Hanley, Charlotte Spencer, Max Emmerich, Camille L. Gérard, Andreas M. Schmitt, Lyra Del Rosario, Eleanor Carlyle, Charlotte B. Lewis, Lucy Holt, Analyn Lucanas, Molly O’Flaherty, Steve Hazell, Hardeep Singh Mudhar, Christina Messiou, Arash Latifoltojar, Annika Fendler, Fiona Byrne, Husayn Pallinkonda, Irene Lobón, Alex Coulton, Anne Laure Cattin, Daqi Deng, Geoffrey Hugang Feng, Andew Rowan, Nadia Yousaf, Sanjay Popat, Olivia Curtis, Charlotte Milner-Watts, Gordon Stamp, Antonia Toncheva, Emma Nye, Aida Murra, Justine Korteweg, D. F. Kelly, Lauren Terry, Jennifer Biano, Kema Peat, Kayleigh Kelly, Peter Hill, Debra H. Josephs, Sheeba Irshad, Ashish Chandra, James Spicer, Ula Mahadeva, Anna Green, Ruby M. Stewart, Lara-Rose Iredale, Tina Mackay, Ben Deakin, Debra Enting, Sarah Rudman, Sharmistha Ghosh, Lena Karapagniotou, Elias Pintus, Andrew Tutt, Sarah Howlett, Vasiliki Michalarea, James D. Brenton, Carlos Caldas, Rebecca C. Fitzgerald, Merche Jimenez-Linan, Elena Provenzano, Alison D. Cluroe, Anna Paterson, Sarah J. Aitken, Kieren Allinson, Grant S. Stewart, Ultan McDermott, Emma Beddowes, Tim Maughan, Olaf Ansorge, Peter J. Campbell, Patricia Roxburgh, Sioban Fraser, Andrew Kidd, Kevin Blyth, John Le Quesne, Matthew Krebs, Fiona Blackhall, Yvonne Summers, Pedro Oliveira, Ana Ortega-Franco, Caroline Dive, Fábio Gomes, Mat Carter, Jo Dransfield, Anne E. Thomas, Dean Fennell, Jacqui Shaw, Babu Naidu, Shobhit Baijal, Bruce Tanchel, Gerald Langman, Andrew Robinson, Martin Collard, Peter Cockcroft, Charlotte Ferris, Hollie Bancroft, Amy Kerr, Gary Middleton, Joanne Webb, Salma Kadiri, Peter Colloby, Bernard Olisemeke, Rodelaine Wilson, Ian Tomlinson, Iain A. McNeish, Sanjay Jogai, Samantha K. Holden, Tânia Rita Moreno de Oliveira Fernandes, Blanche Hampton, Mairead McKenzie, Allan Hackshaw, Abby Sharp, Kitty S. Chan, Laura Farrelly, Hayley Bridger, Rachel Leslie, Mariam Jamal‐Hanjani, Charles Swanton, Mark A. Rubin, Alexander W. Wyatt, Himisha Beltran, Gerhardt Attard, Francesca Demichelis,

Molecular Biology Techniques and Applications

Abstract Sequencing of cell-free DNA (cfDNA) in cancer patients’ plasma offers a minimally-invasive solution to detect tumor cell genomic alterations to aid real-time clinical decision-making. The reliability of copy number detection decreases at lower cfDNA tumor fractions, limiting utility at earlier stages of the disease. To test a novel strategy for detection of allelic imbalance, we developed a prostate cancer bespoke assay, PCF_SELECT, that includes an innovative sequencing panel covering ∼25 000 high minor allele frequency SNPs and tailored analytical solutions to enable allele-informed evaluation. First, we assessed it on plasma samples from 50 advanced prostate cancer patients. We then confirmed improved detection of genomic alterations in samples with <10% tumor fractions when compared against an independent assay. Finally, we applied PCF_SELECT to serial plasma samples intensively collected from three patients previously characterized as harboring alterations involving DNA repair genes and consequently offered PARP inhibition. We identified more extensive pan-genome allelic imbalance than previously recognized in prostate cancer. We confirmed high sensitivity detection of BRCA2 allelic imbalance with decreasing tumor fractions resultant from treatment and identified complex ATM genomic states that may be incongruent with protein losses. Overall, we present a framework for sensitive detection of allele-specific copy number changes in cfDNA.