Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes
James Whitworth(University of Cambridge), Philip Smith(University of Cambridge), Jose‐Ezequiel Martín(University of Cambridge), Hannah D. West(University of Cambridge), Andrea Luchetti(University of Cambridge), Faye Rodger(University of Cambridge), Graeme M. Clark(University of Cambridge), Keren Carss(NHS Blood and Transplant), Jonathan Stephens(NHS Blood and Transplant), Kathleen Stirrups(NHS Blood and Transplant), Chris Penkett(NHS Blood and Transplant), Rutendo Mapeta(NHS Blood and Transplant), Sofie Ashford(Cambridge University Hospitals NHS Foundation Trust), Karyn Mégy(NHS Blood and Transplant), Hassan Shakeel(University of Cambridge), Munaza Ahmed(Great Ormond Street Hospital), Julian Adlard(Chapel Allerton Hospital), Julian Barwell(Leicester Royal Infirmary), Carole Brewer(Royal Devon and Exeter Hospital), Ruth Casey(University of Cambridge), Ruth Armstrong(University of Cambridge), Trevor Cole(Birmingham Women’s and Children’s NHS Foundation Trust), D. Gareth Evans(Manchester Academic Health Science Centre), Florentia Fostira(National Centre of Scientific Research "Demokritos"), Lynn Greenhalgh(University of Liverpool), Helen Hanson(St George's Hospital), Alex Henderson(Centre for Life), Jonathan Hoffman(Birmingham Women’s and Children’s NHS Foundation Trust), Louise Izatt(St Thomas' Hospital), Ajith Kumar(Great Ormond Street Hospital), Ava Kwong(Hong Kong Sanatorium and Hospital), Fiona Lalloo(Manchester Academic Health Science Centre), Kai Ren Ong(Birmingham Women’s and Children’s NHS Foundation Trust), Joan Paterson, Soo‐Mi Park(University of Cambridge), Rakefet Chen‐Shtoyerman(Hadassah Medical Center), Claire Searle(Nottingham University Hospitals NHS Trust), Lucy Side(Great Ormond Street Hospital), Anne‐Bine Skytte(Aarhus University Hospital), Katie Snape(St George's Hospital), Emma R. Woodward(Manchester Academic Health Science Centre), Timothy J. Aitman, Hana Alachkar, Sonia Ali, Louise Allen(St Thomas' Hospital), David Allsup, Gautum Ambegaonkar, Julie Anderson, Richard Antrobus, Ruth Armstrong(University of Cambridge), Gavin Arno, Gururaj Arumugakani, Sofie Ashford(Cambridge University Hospitals NHS Foundation Trust), William F. Astle, Antony Attwood, Steve Austin, Chiara Bacchelli, Tamam Bakchoul, Tadbir K. Bariana, Helen Baxendale(St George's Hospital), David Bennett, Claire Bethune(Nottingham University Hospitals NHS Trust), Shahnaz Bibi, Maria Bitner‐Glindzicz, Marta Bleda, Harm Boggard(University of Cambridge), Paula Bolton‐Maggs, Claire Booth(Nottingham University Hospitals NHS Trust), John R. Bradley, Angie Brady, Matthew A. Brown, Michael J. Browning, Christine Bryson, Siobhan O. Burns, Paul Calleja, Natalie Canham, Jenny Carmichael, Keren Carss(NHS Blood and Transplant), Mark J. Caulfield, Elizabeth Chalmers, Anita Chandra, Patrick F. Chinnery, Manali Chitre, Colin Church, Emma Clement(Manchester Academic Health Science Centre), Emma Clement, Virginia Clowes, Gerry Coghlan, Peter Collins, Victoria Cookson, Nichola Cooper, Paul A. Corris, Amanda Creaser-Myers, Rosa DaCosta, Louise C. Daugherty(St Thomas' Hospital), Sophie Davies, John S. Davis, Minka De Vries, Patrick Deegan, Sri V. V. Deevi, Charu Deshpande, Lisa Devlin, Eleanor Dewhurst, Peter Dixon, Rainer Döffinger, Natalie Dormand, Elizabeth Drewe, David Edgar, William Egner, Wendy N. Erber, Marie Erwood, Marie Erwood, Tamara Everington, Rémi Favier, Helen V. Firth(St George's Hospital), Debra Fletcher, Frances Flinter, Amy Frary, Kathleen Freson(NHS Blood and Transplant), Bruce Furie, Abigail Furnell, Daniel P. Gale, Alice Gardham, Michael Gattens, Neeti Ghali, Pavandeep Ghataorhe, Rohit Ghurye, Simon Gibbs, Kimberley Gilmour, Paul Gissen, Sarah Goddard, Keith Gomez, Pavel Gordins, Stefan Ting Graf, Stefan Ting Graf, Daniel Greene, Alan Greenhalgh(University of Liverpool), Andreas Greinacher, Sofia Grigoriadou, Detelina Grozeva, Scott Hackett, Charaka Hadinnapola, Rosie Hague, Matthias Haimel, Csaba Halmagyi, Tracey Hammerton, Daniel P. Hart, Grant Hayman, Johan W. M. Heemskerk, Robert Henderson(Centre for Life), Anke Hensiek, Yvonne Henskens, Archana Herwadkar, Simon Holden, Muriel Holder, Susan Holder, Fengyuan Hu, Anna Huis in’t Veld(University of Cambridge), Aarnoud Huissoon, Marc Humbert(University of Cambridge), Jane A. Hurst, Roger James(University of Cambridge), Stephen Jolles(NHS Blood and Transplant), Dragana Josifova, Rashid Kazmi, David Keeling, Peter Kelleher, Anne M. Kelly, Fiona Kennedy(Manchester Academic Health Science Centre), David G. Kiely, Nathalie Kingston, Ania Koziell, Deepa Krishnakumar, Taco W. Kuijpers, Taco W. Kuijpers, Dinakantha Kumararatne, Manju A. Kurian, Michael Laffan, Michele P. Lambert, Hana Lango Allen, Hana Lango Allen, Allan Lawrie, Sara Lear, Melissa Lees, Claire Lentaigne(Nottingham University Hospitals NHS Trust), Ri Liesner(NHS Blood and Transplant), Rachel Linger, Hilary Longhurst, Lorena Lorenzo, Eleni Louka, Rajiv D. Machado, Rob Mackenzie Ross, Robert E. MacLaren, Eamonn R. Maher(University of Cambridge), Jesmeen Maimaris, Sarah Mangles, Ania Manson, Rutendo Mapeta(NHS Blood and Transplant), Hugh S. Markus, Jennifer C. Martin(University of Cambridge), Larahmie Masati, Mary Mathias, Vera Matser, Anna Maw(University of Cambridge), Elizabeth McDermott, Coleen McJannet, Stuart Meacham, Sharon Meehan, Karyn Mégy(NHS Blood and Transplant), Sarju Mehta, Michel Michaelides, Carolyn M. Millar, Shahin Moledina, Anthony T. Moore, Nicholas W. Morrell, Andrew Mumford, Sai Murng, Elaine Murphy, Sergey Nejentsev, Sadia Noorani, Paquita Nurden, Éric Oksenhendler, Shokri Othman, Willem H. Ouwehand, Willem H. Ouwehand, Sofia Papadia, Soo‐Mi Park(University of Cambridge), Alasdair Parker, John Pasi, Christine Patch(NHS Blood and Transplant), Joan Paterson, Jeanette Payne, Andrew J. Peacock, Kathelijne Peerlinck, Christopher J. Penkett(NHS Blood and Transplant), Joanna Pepke‐Żaba, David J. Perry, David J. Perry, Val Pollock, Gary Polwarth, Mark Ponsford, Waseem Qasim, Isabella Quinti, Stuart Rankin, Julia Rankin(Leicester Royal Infirmary), F. Lucy Raymond, Paula Rayner-Matthews, Karola Rehnström, Evan Reid(Manchester Academic Health Science Centre), Christopher J. Rhodes, Michael Richards, Sylvia Richardson, Alex Richter(Centre for Life), Irene Roberts, Matthew T. Rondina, Elisabeth Rosser, Catherine Roughley, Noémi Roy, Kévin Rue-Albrecht, Crina Samarghitean, Alba Sanchis‐Juan, Richard Sandford, Saikat Santra, Ravishankar Sargur, Sinisa Savic, Gwen Schotte, Sol Schulman, Harald Schulze, Richard H. Scott, Marie Scully, Suranjith L. Seneviratne, Carrock Sewell, Olga Shamardina, Debbie Shipley, Ilenia Simeoni, Suthesh Sivapalaratnam, Kenneth G. C. Smith(University of Cambridge), Aman Sohal, Laura Southgate, Simon Staines, Emily Staples, Hannah Stark(University of Cambridge), Hans J. Stauss(St George's Hospital), Penelope E. Stein, Jonathan Stephens(NHS Blood and Transplant), Kathleen Stirrups(NHS Blood and Transplant), Sophie Stock, Jay Suntharalingam, Kate Talks, Yvonne Tan, Jecko Thachil, James Thaventhiran(University of Cambridge), Ellen Thomas, Moira Thomas, Dorothy Thompson, Adrian J. Thrasher, Marc Tischkowitz(University of Cambridge), Catherine Titterton, Cheng‐Hock Toh, Mark Toshner, Carmen Treacy, Richard C. Trembath, Salih Tuna, Wojciech Turek, Ernest Turro, Chris Van Geet(NHS Blood and Transplant), Marijke Veltman, Julie Vogt, Julie von Ziegenweldt, Anton Vonk Noordegraaf, Emma Wakeling(Manchester Academic Health Science Centre), Ivy Wanjiku, Timothy Q. Warner, Evangeline Wassmer, Hugh Watkins, Christopher D. Watt, ndrew Webster, Steve Welch, Sarah K. Westbury, John Wharton, Deborah Whitehorn, Martin Wilkins(University of Cambridge), Lisa Willcocks, Catherine Williamson, Geoffrey Woods, Geoff Woods, John Wort(University of Cambridge), Nigel Yeatman, Patrick Yong, Timothy M. Young, Ping Yu, Marc Tischkowitz(University of Cambridge), Eamonn R. Maher(University of Cambridge)
Cited by 73Open Access
Abstract
= 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.