Allele-informed copy number evaluation of plasma DNA samples from metastatic prostate cancer patients: the PCF_SELECT consortium assay
Creators: name: Orlando, Francesco
name: Romanel, Alessandro
name: Trujillo, Blanca
name: Sigouros, Michael
name: Wetterskog, Daniel
name: Quaini, Orsetta
name: Leone, Gianmarco
name: Xiang, Jenny Z
name: Wingate, Anna
name: Tagawa, Scott
name: Jayaram, Anuradha
name: Linch, Mark
name: Swanton, Charles
name: Jamal-Hanjani, Mariam
name: Abbosh, Chris
name: Zaccaria, Simone
name: Hessey, Sonya
name: Shiu, Kai-Keen
name: Bridgewater, John
name: Hochhauser, Daniel
name: Forster, Martin
name: Lee, Siow-Ming
name: Ahmad, Tanya
name: Papadatos-Pastos, Dionysis
name: Janes, Sam
name: Van Loo, Peter
name: Enfield, Katey
name: McGranahan, Nicholas
name: Huebner, Ariana
name: Quezada, Sergio
name: Beck, Stephan
name: Parker, Peter
name: Enver, Tariq
name: Hynds, Robert E
name: Dijkstra, Krijn
name: Pearce, David R
name: Falzon, Mary
name: Proctor, Ian
name: Sinclair, Ron
name: Lok, Chi-wah
name: Rhodes, Zoe
name: Moore, David
name: Marafioti, Teresa
name: Mitchison, Miriam
name: Ellery, Peter
name: Sivakumar, Monica
name: Brandner, Sebastian
name: Rowan, Andrew
name: Hiley, Crispin
name: Veeriah, Selvaraju
name: Shaw, Heather
name: Attard, Gert
name: Naceur-Lombardelli, Cristina
name: Toncheva, Antonia
name: Prymas, Paulina
name: Watkins, Tom
name: Bailey, Chris
name: Ruiz, Carlos Martinez
name: Litchfield, Kevin
name: Al-Bakir, Maise
name: Kanu, Nnenna
name: Ward, Sophie
name: Lim, Emilia
name: Reading, James
name: Chain, Benny
name: Alba, Blanca Trujillo
name: Akay, Melek
name: Flanagan, Adrienne
name: Biswas, Dhruva
name: Pich, Oriol
name: Dietzen, Michelle
name: Puttick, Clare
name: Colliver, Emma
name: Magness, Alistair
name: Angelova, Mihaela
name: Black, James
name: Lucas, Olivia
name: Hill, William
name: Liu, Wing-Kin
name: Frankell, Alexander
name: Magno, Neil
name: Athanasopoulou, Foteini
name: Wilson, Gareth
name: Rosenthal, Rachel
name: Salgado, Roberto
name: Lee, Claudia
name: Grigoriadis, Kristiana
name: Al-Sawaf, Othman
name: Karasaki, Takahiro
name: Bunkum, Abigail
name: Noorani, Imran
name: Benafif, Sarah
name: Barbe, Vittorio
name: Bola, Supreet
name: Vainauskas, Osvaldas
name: Hasan, Mahedi
name: Lise, Stefano
name: Leone, GianMarco
name: Alifrangis, Constantine
name: McGovern, Ursula
name: Thol, Kerstin
name: Gamble, Samuel
name: Ung, Seng Kuong
name: Sahwangarrom, Teerapon
name: Marin, Claudia Peinador
name: Wong, Sophia
name: Pawlik, Piotr
name: Gishen, Faye
name: Tookman, Adrian
name: Stone, Paddy
name: Stirling, Caroline
name: Turajlic, Samra
name: Larkin, James
name: Pickering, Lisa
name: Furness, Andrew
name: Young, Kate
name: Drake, Will
name: Edmonds, Kim
name: Hunter, Nikki
name: Mangwende, Mary
name: Pearce, Karla
name: Grostate, Lauren
name: Au, Lewis
name: Spain, Lavinia
name: Shepherd, Scott
name: Yan, Haixi
name: Shum, Ben
name: Tippu, Zayd
name: Hanley, Brian
name: Spencer, Charlotte
name: Emmerich, Max
name: Gerard, Camille
name: Schmitt, Andreas Michael
name: Del Rosario, Lyra
name: Carlyle, Eleanor
name: Lewis, Charlotte
name: Holt, Lucy
name: Lucanas, Analyn
name: O'Flaherty, Molly
name: Hazell, Steve
name: Mudhar, Hardeep
name: Messiou, Christina
name: Latifoltojar, Arash
name: Fendler, Annika
name: Byrne, Fiona
name: Pallinkonda, Husayn
name: Lobon, Irene
name: Coulton, Alex
name: Cattin, Anne Laure
name: Deng, Daqi
name: Feng, Geoffrey Hugang
name: Rowan, Andew
name: Yousaf, Nadia
name: Popat, Sanjay
name: Curtis, Olivia
name: Milner-Watts, Charlotte
name: Stamp, Gordon
name: Nye, Emma
name: Murra, Aida
name: Korteweg, Justine
name: Kelly, Denise
name: Terry, Lauren
name: Biano, Jennifer
name: Peat, Kema
name: Kelly, Kayleigh
name: Hill, Peter
name: Josephs, Debra
name: Irshad, Sheeba
name: Chandra, Ashish
name: Spicer, James
name: Mahadeva, Ula
name: Green, Anna
name: Stewart, Ruby
name: Iredale, Lara-Rose
name: Mackay, Tina
name: Deakin, Ben
name: Enting, Debra
name: Rudman, Sarah
name: Ghosh, Sharmistha
name: Karapagniotou, Lena
name: Pintus, Elias
name: Tutt, Andrew
name: Howlett, Sarah
name: Michalarea, Vasiliki
name: Brenton, James
name: Caldas, Carlos
name: Fitzgerald, Rebecca
name: Jimenez-Linan, Merche
name: Provenzano, Elena
name: Cluroe, Alison
name: Paterson, Anna
name: Aitken, Sarah
name: Allinson, Kieren
name: Stewart, Grant
name: McDermott, Ultan
name: Beddowes, Emma
name: Maughan, Tim
name: Ansorge, Olaf
name: Campbell, Peter
name: Roxburgh, Patricia
name: Fraser, Sioban
name: Kidd, Andrew
name: Blyth, Kevin
name: Le Quesne, John
name: Krebs, Matthew
name: Blackhall, Fiona
name: Summers, Yvonne
name: Oliveira, Pedro
name: Ortega-Franco, Ana
name: Dive, Caroline
name: Gomes, Fabio
name: Carter, Mat
name: Dransfield, Jo
name: Thomas, Anne
name: Fennell, Dean
name: Shaw, Jacqui
name: Naidu, Babu
name: Baijal, Shobhit
name: Tanchel, Bruce
name: Langman, Gerald
name: Robinson, Andrew
name: Collard, Martin
name: Cockcroft, Peter
name: Ferris, Charlotte
name: Bancroft, Hollie
name: Kerr, Amy
name: Middleton, Gary
name: Webb, Joanne
name: Kadiri, Salma
name: Colloby, Peter
name: Olisemeke, Bernard
name: Wilson, Rodelaine
name: Tomlinson, Ian
name: McNeish, Iain
name: Jogai, Sanjay
name: Holden, Samantha
name: Fernandes, Tania
name: Hampton, Blanche
name: McKenzie, Mairead
name: Hackshaw, Allan
name: Sharp, Abby
name: Chan, Kitty
name: Farrelly, Laura
name: Bridger, Hayley
name: Leslie, Rachel
name: Consortium, PEACE
name: Rubin, Mark A
name: Wyatt, Alexander W
name: Beltran, Himisha
name: Attard, Gerhardt
name: Demichelis, Francesca
Publisher: name: The Francis Crick Institute
Year: 2022
Subjects: classificationCode: Tumour Biology
subject: Tumour Biology
classificationCode: Signalling & Oncogenes
subject: Signalling &amp; Oncogenes
classificationCode: Genetics & Genomics
subject: Genetics &amp; Genomics
classificationCode: Genome Integrity & Repair
subject: Genome Integrity &amp; Repair
classificationCode: Human Biology & Physiology
subject: Human Biology &amp; Physiology
classificationCode: Chemical Biology & High Throughput
subject: Chemical Biology &amp; High Throughput
classificationCode: Ecology,Evolution & Ethology
subject: Ecology,Evolution &amp; Ethology
classificationCode: Computational & Systems Biology
subject: Computational &amp; Systems Biology

description: 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 &lt;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.