Journal Articles Cell Reports Year : 2020

Representative sequencing: Unbiased sampling of solid tumor tissue

Kevin Litchfield (1) , Stacey Stanislaw , Lisa Gallegos , Andrew Rowan (2) , Desiree Schnidrig , Heidi Rosenbaum , Alexandre Harlé (3) , Lewis Au (4) , Samantha Hill (5) , Zayd Tippu , Jennifer Thomas , Lisa Thompson , Hang Xu , Stuart Horswell , Aoune Barhoumi , Carol Jones (6) , Katherine Leith , Daniel Burgess , Thomas B.K. Watkins , Nicolai Juul Birkbak (7) , Philippe Lamy (8) , Iver Nordentoft , Lars Dyrskjøt (9) , Lisa Pickering , Stephen Hazell , Mariam Jamal-Hanjani (10) , James J Larkin (11) , Charles Swanton (10) , Nelson r. Alexander , Samra Turajlic , Chris Abbosh , Kai-Keen Shiu , John Bridgewater (12) , Daniel Hochhauser , Martin Forster , Siow-Ming Lee , Tanya Ahmad , Dionysis Papadatos-Pastos , Sam Janes , Peter van Loo (13) , Katey Enfield , Nicholas Mcgranahan , Ariana Huebner , Sergio Quezada , Stephan Beck , Peter Parker , Henning Walczak , Tariq Enver , Rob Hynds , Mary Falzon , Ian Proctor (14) , Ron Sinclair , Chi-Wah Lok , Zoe Rhodes , David Moore (15) , Teresa Marafioti (16) , Elaine Borg , Miriam Mitchison , Reena Khiroya , Giorgia Trevisan , Peter Ellery , Mark Linch , Sebastian Brandner (17) , Crispin Hiley , Selvaraju Veeriah , Maryam Razaq , Heather Shaw , Gert Attard , Mita Afroza Akther , Cristina Naceur-Lombardelli , Lizi Manzano , Maise Al-Bakir , Simranpreet Summan , Nnenna Kanu , Sophie Ward , Uzma Asghar , Emilia Lim , Faye Gishen , Adrian Tookman , Paddy Stone , Caroline Stirling , Andrew Furness , Kim Edmonds , Nikki Hunter , Sarah Sarker , Sarah Vaughan , Mary Mangwende , Karla Pearce , Lavinia Spain , Scott Shepherd , Haixi Yan , Ben Shum , Eleanor Carlyle , Steve Hazell , Annika Fendler , Fiona Byrne (18) , Nadia Yousaf , Sanjay Popat , Olivia Curtis , Gordon Stamp (19) , Antonia Toncheva , Emma Nye (17) , Aida Murra , Justine Korteweg , Nahid Sheikh , Debra Josephs , Ashish Chandra (20) , James Spicer , Ula Mahadeva , Anna Green , Ruby Stewart , Lara-Rose Iredale , Tina Mackay , Ben Deakin , Debra Enting , Sarah Rudman , Sharmistha Ghosh , Lena Karapagniotou , Elias Pintus , Andrew Tutt (21) , Sarah Howlett , Vasiliki Michalarea , James Brenton , Carlos Caldas (22) , Rebecca Fitzgerald , Merche Jimenez-Linan , Elena Provenzano , Alison Cluroe , Grant Stewart , Colin Watts , Richard Gilbertson , Ultan Mcdermott , Simon Tavare , Emma Beddowes , Patricia Roxburgh , Andrew Biankin (23) , Anthony Chalmers , Sioban Fraser , Karin Oien , Andrew Kidd , Kevin Blyth , Matt Krebs , Fiona Blackhall , Yvonne Summers , Caroline Dive (24) , Richard Marais (25) , Fabio Gomes , Mat Carter , Jo Dransfield , John Le Quesne (26) , 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 (27) , Sanjay Jogai , Christian Ottensmeier (28) , David L Harrison (29) , Massimo Loda , Adrienne Flanagan , Mairead Mckenzie , Allan Hackshaw , Jonathan Ledermann , Abby Sharp , Laura Farrelly , Hayley Bridger
Stacey Stanislaw
  • Function : Author
Lisa Gallegos
  • Function : Author
Desiree Schnidrig
  • Function : Author
Heidi Rosenbaum
  • Function : Author
Lewis Au
  • Function : Author
Samantha Hill
Zayd Tippu
  • Function : Author
Jennifer Thomas
  • Function : Author
Lisa Thompson
  • Function : Author
Hang Xu
  • Function : Author
Stuart Horswell
  • Function : Author
Aoune Barhoumi
  • Function : Author
Carol Jones
  • Function : Author
  • PersonId : 862466
Katherine Leith
  • Function : Author
Daniel Burgess
  • Function : Author
Thomas B.K. Watkins
  • Function : Author
Iver Nordentoft
  • Function : Author
Lars Dyrskjøt
  • Function : Author
  • PersonId : 1036778
Lisa Pickering
  • Function : Author
Stephen Hazell
  • Function : Author
Nelson r. Alexander
  • Function : Author
Samra Turajlic
  • Function : Author
Chris Abbosh
  • Function : Author
Kai-Keen Shiu
  • Function : Author
Daniel Hochhauser
  • Function : Author
Martin Forster
  • Function : Author
Siow-Ming Lee
  • Function : Author
Tanya Ahmad
  • Function : Author
Dionysis Papadatos-Pastos
  • Function : Author
Sam Janes
  • Function : Author
Katey Enfield
  • Function : Author
Nicholas Mcgranahan
  • Function : Author
Ariana Huebner
  • Function : Author
Sergio Quezada
  • Function : Author
Stephan Beck
  • Function : Author
Peter Parker
  • Function : Author
Henning Walczak
  • Function : Author
Tariq Enver
  • Function : Author
Rob Hynds
  • Function : Author
Mary Falzon
  • Function : Author
Ian Proctor
  • Function : Author
  • PersonId : 903035
Ron Sinclair
  • Function : Author
Chi-Wah Lok
  • Function : Author
Zoe Rhodes
  • Function : Author
Elaine Borg
  • Function : Author
Miriam Mitchison
  • Function : Author
Reena Khiroya
  • Function : Author
Giorgia Trevisan
  • Function : Author
Peter Ellery
  • Function : Author
Mark Linch
  • Function : Author
Crispin Hiley
  • Function : Author
Selvaraju Veeriah
  • Function : Author
Maryam Razaq
  • Function : Author
Heather Shaw
  • Function : Author
Gert Attard
  • Function : Author
Mita Afroza Akther
  • Function : Author
Cristina Naceur-Lombardelli
  • Function : Author
Lizi Manzano
  • Function : Author
Maise Al-Bakir
  • Function : Author
Simranpreet Summan
  • Function : Author
Nnenna Kanu
  • Function : Author
Sophie Ward
  • Function : Author
Uzma Asghar
  • Function : Author
Emilia Lim
  • Function : Author
Faye Gishen
  • Function : Author
Adrian Tookman
  • Function : Author
Paddy Stone
  • Function : Author
Caroline Stirling
  • Function : Author
Andrew Furness
  • Function : Author
Kim Edmonds
  • Function : Author
Nikki Hunter
  • Function : Author
Sarah Sarker
  • Function : Author
Sarah Vaughan
  • Function : Author
Mary Mangwende
  • Function : Author
Karla Pearce
  • Function : Author
Lavinia Spain
  • Function : Author
Scott Shepherd
  • Function : Author
Haixi Yan
  • Function : Author
Ben Shum
  • Function : Author
Eleanor Carlyle
  • Function : Author
Steve Hazell
  • Function : Author
Annika Fendler
  • Function : Author
Nadia Yousaf
  • Function : Author
Sanjay Popat
  • Function : Author
Olivia Curtis
  • Function : Author
Antonia Toncheva
  • Function : Author
Aida Murra
  • Function : Author
Justine Korteweg
  • Function : Author
Nahid Sheikh
  • Function : Author
Debra Josephs
  • Function : Author
James Spicer
  • Function : Author
Ula Mahadeva
  • Function : Author
Anna Green
  • Function : Author
Ruby Stewart
  • Function : Author
Lara-Rose Iredale
  • Function : Author
Tina Mackay
  • Function : Author
Ben Deakin
  • Function : Author
Debra Enting
  • Function : Author
Sarah Rudman
  • Function : Author
Sharmistha Ghosh
  • Function : Author
Lena Karapagniotou
  • Function : Author
Elias Pintus
  • Function : Author
Sarah Howlett
  • Function : Author
Vasiliki Michalarea
  • Function : Author
James Brenton
  • Function : Author
Rebecca Fitzgerald
  • Function : Author
Merche Jimenez-Linan
  • Function : Author
Elena Provenzano
Alison Cluroe
  • Function : Author
Grant Stewart
  • Function : Author
Colin Watts
  • Function : Author
Richard Gilbertson
  • Function : Author
Ultan Mcdermott
  • Function : Author
Simon Tavare
  • Function : Author
Emma Beddowes
  • Function : Author
Patricia Roxburgh
  • Function : Author
Anthony Chalmers
  • Function : Author
Sioban Fraser
  • Function : Author
Karin Oien
  • Function : Author
Andrew Kidd
  • Function : Author
Kevin Blyth
  • Function : Author
Matt Krebs
  • Function : Author
Fiona Blackhall
  • Function : Author
Yvonne Summers
  • Function : Author
Caroline Dive
  • Function : Author
  • PersonId : 882488
Fabio Gomes
  • Function : Author
Mat Carter
  • Function : Author
Jo Dransfield
  • Function : Author
Dean Fennell
  • Function : Author
Jacqui Shaw
  • Function : Author
Babu Naidu
  • Function : Author
Shobhit Baijal
  • Function : Author
Bruce Tanchel
  • Function : Author
Gerald Langman
  • Function : Author
Andrew Robinson
  • Function : Author
Martin Collard
  • Function : Author
Peter Cockcroft
  • Function : Author
Charlotte Ferris
  • Function : Author
Hollie Bancroft
  • Function : Author
Amy Kerr
  • Function : Author
Gary Middleton
  • Function : Author
Joanne Webb
  • Function : Author
Salma Kadiri
  • Function : Author
Peter Colloby
  • Function : Author
Bernard Olisemeke
  • Function : Author
Rodelaine Wilson
  • Function : Author
Sanjay Jogai
  • Function : Author
Christian Ottensmeier
  • Function : Author
  • PersonId : 924511
Massimo Loda
  • Function : Author
Adrienne Flanagan
  • Function : Author
Mairead Mckenzie
  • Function : Author
Allan Hackshaw
  • Function : Author
Jonathan Ledermann
  • Function : Author
Abby Sharp
  • Function : Author
Laura Farrelly
  • Function : Author
Hayley Bridger
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Abstract

Although thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias isinherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g., 6 mmbiopsy), which becomes grossly under-powered as tumor volume scales. Here, we demonstrate representative sequencing (Rep-Seq) as a new method to achieve unbiased tumor tissue sampling. Rep-Seq uses fixed residual tumor material, which is homogenized and subjected to next-generation sequencing. Analysis of intratumor tumor mutation burden (TMB) variability shows a high level of misclassification using current single-biopsy methods, with 20% of lung and 52% of bladder tumors having at least one biopsy with high TMB butlow clonal TMB overall. Misclassification rates by contrast are reduced to 2% (lung) and 4% (bladder) when a more representative sampling methodology is used. Rep-Seq offers an improved sampling protocol for tumor profiling, with significant potential for improved clinical utility and more accurate deconvolution of clonal structure.

Domains

Cancer

Dates and versions

hal-02565183 , version 1 (06-05-2020)

Identifiers

Cite

Kevin Litchfield, Stacey Stanislaw, Lisa Gallegos, Andrew Rowan, Desiree Schnidrig, et al.. Representative sequencing: Unbiased sampling of solid tumor tissue. Cell Reports, 2020, 31 (5), pp.107550. ⟨10.1016/j.celrep.2020.107550⟩. ⟨hal-02565183⟩
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