Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling.
Humans
Tumor Suppressor Protein p53
/ genetics
Animals
Chromosomal Instability
Mice
Lung Neoplasms
/ genetics
ErbB Receptors
/ genetics
Mutation
Drug Resistance, Neoplasm
/ genetics
Cell Line, Tumor
Protein Kinase Inhibitors
/ pharmacology
Adenocarcinoma of Lung
/ genetics
Molecular Targeted Therapy
/ methods
Female
DNA Copy Number Variations
Male
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 Jun 2024
13 Jun 2024
Historique:
received:
12
09
2023
accepted:
28
03
2024
medline:
14
6
2024
pubmed:
14
6
2024
entrez:
13
6
2024
Statut:
epublish
Résumé
The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone. The combined presence of whole genome doubling (WGD) and TP53 co-mutations leads to increased genome instability and genomic copy number aberrations in genes implicated in EGFR TKI resistance. Using mouse models and an in vitro isogenic p53-mutant model system, we provide evidence that WGD provides diverse routes to drug resistance by increasing the probability of acquiring copy-number gains or losses relative to non-WGD cells. These data provide a molecular basis for mixed tumor responses to targeted therapy, within an individual patient, with implications for therapeutic strategies.
Identifiants
pubmed: 38871738
doi: 10.1038/s41467-024-47606-9
pii: 10.1038/s41467-024-47606-9
doi:
Substances chimiques
Tumor Suppressor Protein p53
0
ErbB Receptors
EC 2.7.10.1
TP53 protein, human
0
Protein Kinase Inhibitors
0
EGFR protein, human
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4871Subventions
Organisme : Wellcome Trust
ID : FC001169
Pays : United Kingdom
Organisme : Cancer Research UK (CRUK)
ID : C416/A21999
Organisme : Cancer Research UK (CRUK)
ID : C11496/A30025
Organisme : Wellcome Trust
ID : FC001169
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001169
Pays : United Kingdom
Organisme : Royal Society
ID : RSRP\R\210001
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : ID16584
Organisme : EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))
ID : 617844
Organisme : EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))
ID : 617844
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 835297
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 835297
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 835297
Investigateurs
Jason F Lester
(JF)
Amrita Bajaj
(A)
Apostolos Nakas
(A)
Azmina Sodha-Ramdeen
(A)
Mohamad Tufail
(M)
Molly Scotland
(M)
Rebecca Boyles
(R)
Sridhar Rathinam
(S)
Claire Wilson
(C)
Domenic Marrone
(D)
Sean Dulloo
(S)
Dean A Fennell
(DA)
Gurdeep Matharu
(G)
Jacqui A Shaw
(JA)
Ekaterini Boleti
(E)
Heather Cheyne
(H)
Mohammed Khalil
(M)
Shirley Richardson
(S)
Tracey Cruickshank
(T)
Gillian Price
(G)
Keith M Kerr
(KM)
Sarah Benafif
(S)
Jack French
(J)
Kayleigh Gilbert
(K)
Babu Naidu
(B)
Akshay J Patel
(AJ)
Aya Osman
(A)
Carol Enstone
(C)
Gerald Langman
(G)
Helen Shackleford
(H)
Madava Djearaman
(M)
Salma Kadiri
(S)
Gary Middleton
(G)
Angela Leek
(A)
Jack Davies Hodgkinson
(JD)
Nicola Totton
(N)
Angeles Montero
(A)
Elaine Smith
(E)
Eustace Fontaine
(E)
Felice Granato
(F)
Antonio Paiva-Correia
(A)
Juliette Novasio
(J)
Kendadai Rammohan
(K)
Leena Joseph
(L)
Paul Bishop
(P)
Rajesh Shah
(R)
Stuart Moss
(S)
Vijay Joshi
(V)
Philip A J Crosbie
(PAJ)
Katherine D Brown
(KD)
Mathew Carter
(M)
Anshuman Chaturvedi
(A)
Pedro Oliveira
(P)
Colin R Lindsay
(CR)
Fiona H Blackhall
(FH)
Matthew G Krebs
(MG)
Yvonne Summers
(Y)
Alexandra Clipson
(A)
Jonathan Tugwood
(J)
Alastair Kerr
(A)
Dominic G Rothwell
(DG)
Caroline Dive
(C)
Hugo J W L Aerts
(HJWL)
Roland F Schwarz
(RF)
Tom L Kaufmann
(TL)
Gareth A Wilson
(GA)
Rachel Rosenthal
(R)
Peter Van Loo
(P)
Nicolai J Birkbak
(NJ)
Zoltan Szallasi
(Z)
Judit Kisistok
(J)
Mateo Sokac
(M)
Roberto Salgado
(R)
Miklos Diossy
(M)
Jonas Demeulemeester
(J)
Abigail Bunkum
(A)
Angela Dwornik
(A)
Alastair Magness
(A)
Andrew J Rowan
(AJ)
Angeliki Karamani
(A)
Antonia Toncheva
(A)
Benny Chain
(B)
Carla Castignani
(C)
Chris Bailey
(C)
Christopher Abbosh
(C)
Clare Puttick
(C)
Clare E Weeden
(CE)
Claudia Lee
(C)
Corentin Richard
(C)
Cristina Naceur-Lombardelli
(C)
David R Pearce
(DR)
Despoina Karagianni
(D)
Dhruva Biswas
(D)
Dina Levi
(D)
Elizabeth Larose Cadieux
(E)
Emilia L Lim
(EL)
Emma Colliver
(E)
Emma Nye
(E)
Felip Gálvez-Cancino
(F)
Francisco Gimeno-Valiente
(F)
George Kassiotis
(G)
Georgia Stavrou
(G)
Gerasimos-Theodoros Mastrokalos
(GT)
Helen L Lowe
(HL)
Ignacio Garcia Matos
(IG)
Imran Noorani
(I)
Jacki Goldman
(J)
James L Reading
(JL)
Jayant K Rane
(JK)
Jerome Nicod
(J)
John A Hartley
(JA)
Karl S Peggs
(KS)
Katey S S Enfield
(KSS)
Kayalvizhi Selvaraju
(K)
Kerstin Thol
(K)
Kevin W Ng
(KW)
Kezhong Chen
(K)
Krijn Dijkstra
(K)
Kristiana Grigoriadis
(K)
Krupa Thakkar
(K)
Leah Ensell
(L)
Mansi Shah
(M)
Maria Litovchenko
(M)
Mariam Jamal-Hanjani
(M)
Mariana Werner Sunderland
(M)
Matthew R Huska
(MR)
Mark S Hill
(MS)
Michelle Dietzen
(M)
Michelle M Leung
(MM)
Mickael Escudero
(M)
Miljana Tanić
(M)
Monica Sivakumar
(M)
Olga Chervova
(O)
Olivia Lucas
(O)
Oriol Pich
(O)
Othman Al-Sawaf
(O)
Paulina Prymas
(P)
Philip Hobson
(P)
Piotr Pawlik
(P)
Richard Kevin Stone
(RK)
Robert Bentham
(R)
Roberto Vendramin
(R)
Sadegh Saghafinia
(S)
Samuel Gamble
(S)
Selvaraju Veeriah
(S)
Seng Kuong Anakin Ung
(SKA)
Sergio A Quezada
(SA)
Sharon Vanloo
(S)
Sonya Hessey
(S)
Sophia Ward
(S)
Sian Harries
(S)
Stefan Boeing
(S)
Stephan Beck
(S)
Supreet Kaur Bola
(SK)
Takahiro Karasaki
(T)
Tamara Denner
(T)
Teresa Marafioti
(T)
Thomas Patrick Jones
(TP)
Victoria Spanswick
(V)
Vittorio Barbè
(V)
Wei-Ting Lu
(WT)
Wing Kin Liu
(WK)
Yin Wu
(Y)
Yutaka Naito
(Y)
Zoe Ramsden
(Z)
Catarina Veiga
(C)
Gary Royle
(G)
Charles-Antoine Collins-Fekete
(CA)
Francesco Fraioli
(F)
Paul Ashford
(P)
Martin D Forster
(MD)
Siow Ming Lee
(SM)
Elaine Borg
(E)
Mary Falzon
(M)
Dionysis Papadatos-Pastos
(D)
James Wilson
(J)
Tanya Ahmad
(T)
Alexander James Procter
(AJ)
Asia Ahmed
(A)
Magali N Taylor
(MN)
Arjun Nair
(A)
David Lawrence
(D)
Davide Patrini
(D)
Neal Navani
(N)
Ricky M Thakrar
(RM)
Sam M Janes
(SM)
Emilie Martinoni Hoogenboom
(E)
Fleur Monk
(F)
James W Holding
(JW)
Junaid Choudhary
(J)
Kunal Bhakhri
(K)
Marco Scarci
(M)
Pat Gorman
(P)
Reena Khiroya
(R)
Robert C M Stephens
(RCM)
Yien Ning Sophia Wong
(YNS)
Zoltan Kaplar
(Z)
Steve Bandula
(S)
Allan Hackshaw
(A)
Anne-Marie Hacker
(AM)
Abigail Sharp
(A)
Sean Smith
(S)
Harjot Kaur Dhanda
(H)
Camilla Pilotti
(C)
Rachel Leslie
(R)
Anca Grapa
(A)
Hanyun Zhang
(H)
Khalid AbdulJabbar
(K)
Xiaoxi Pan
(X)
Yinyin Yuan
(Y)
David Chuter
(D)
Mairead MacKenzie
(M)
Serena Chee
(S)
Aiman Alzetani
(A)
Judith Cave
(J)
Jennifer Richards
(J)
Eric Lim
(E)
Paulo De Sousa
(P)
Simon Jordan
(S)
Alexandra Rice
(A)
Hilgardt Raubenheimer
(H)
Harshil Bhayani
(H)
Lyn Ambrose
(L)
Anand Devaraj
(A)
Hema Chavan
(H)
Sofina Begum
(S)
Silviu I Buderi
(SI)
Daniel Kaniu
(D)
Mpho Malima
(M)
Sarah Booth
(S)
Andrew G Nicholson
(AG)
Nadia Fernandes
(N)
Pratibha Shah
(P)
Chiara Proli
(C)
Madeleine Hewish
(M)
Sarah Danson
(S)
Michael J Shackcloth
(MJ)
Lily Robinson
(L)
Peter Russell
(P)
Kevin G Blyth
(KG)
Andrew Kidd
(A)
Craig Dick
(C)
John Le Quesne
(J)
Alan Kirk
(A)
Mo Asif
(M)
Rocco Bilancia
(R)
Nikos Kostoulas
(N)
Mathew Thomas
(M)
Informations de copyright
© 2024. The Author(s).
Références
Cancer Genome Atlas Research, N. Comprehensive molecular profiling of lung adenocarcinoma. Nature 511, 543–550 (2014).
doi: 10.1038/nature13385
Cho, J. et al. Proportion and clinical features of never-smokers with non-small cell lung cancer. Chin. J. Cancer 36, 20 (2017).
pubmed: 28179026
pmcid: 5299770
doi: 10.1186/s40880-017-0187-6
Kohsaka, S., Petronczki, M., Solca, F. & Maemondo, M. Tumor clonality and resistance mechanisms in EGFR mutation-positive non-small-cell lung cancer: implications for therapeutic sequencing. Future Oncol. 15, 637–652 (2019).
pubmed: 30404555
doi: 10.2217/fon-2018-0736
Wu, S. G. & Shih, J. Y. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol. Cancer 17, 38 (2018).
pubmed: 29455650
pmcid: 5817870
doi: 10.1186/s12943-018-0777-1
Gelatti, A. C. Z., Drilon, A. & Santini, F. C. Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Lung Cancer 137, 113–122 (2019).
pubmed: 31568888
doi: 10.1016/j.lungcan.2019.09.017
Mok, T. S. et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N. Engl. J. Med. 376, 629–640 (2017).
pubmed: 27959700
doi: 10.1056/NEJMoa1612674
Soria, J. C. et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N. Engl. J. Med. 378, 113–125 (2018).
pubmed: 29151359
doi: 10.1056/NEJMoa1713137
Therasse, P. et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J. Natl Cancer Inst. 92, 205–216 (2000).
pubmed: 10655437
doi: 10.1093/jnci/92.3.205
Schwartz, L. H. et al. RECIST 1.1-update and clarification: from the RECIST committee. Eur. J. Cancer 62, 132–137 (2016).
pubmed: 27189322
pmcid: 5737828
doi: 10.1016/j.ejca.2016.03.081
Jackman, D. et al. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J. Clin. Oncol. 28, 357–360 (2010).
pubmed: 19949011
doi: 10.1200/JCO.2009.24.7049
Engelman, J. A. & Janne, P. A. Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Clin. Cancer Res. 14, 2895–2899 (2008).
pubmed: 18483355
doi: 10.1158/1078-0432.CCR-07-2248
Roper, N. et al. Clonal evolution and heterogeneity of osimertinib acquired resistance mechanisms in EGFR mutant lung cancer. Cell Rep. Med. 1, 100007 (2020).
Leonetti, A. et al. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br. J. Cancer 121, 725–737 (2019).
pubmed: 31564718
pmcid: 6889286
doi: 10.1038/s41416-019-0573-8
Rios-Hoyo, A., Moliner, L. & Arriola, E. Acquired mechanisms of resistance to osimertinib-the next challenge. Cancers 14, 1931 (2022).
Reiter, J. G. et al. An analysis of genetic heterogeneity in untreated cancers. Nat. Rev. Cancer 19, 639–650 (2019).
pubmed: 31455892
pmcid: 6816333
doi: 10.1038/s41568-019-0185-x
Crusz, S. M. et al. Heterogeneous response and progression patterns reveal phenotypic heterogeneity of tyrosine kinase inhibitor response in metastatic renal cell carcinoma. BMC Med. 14, 185 (2016).
pubmed: 27842541
pmcid: 5108081
doi: 10.1186/s12916-016-0729-9
van Kessel, C. S. et al. Radiological heterogeneity in response to chemotherapy is associated with poor survival in patients with colorectal liver metastases. Eur. J. Cancer 49, 2486–2493, (2013).
pubmed: 23692811
doi: 10.1016/j.ejca.2013.03.027
Humbert, O. & Chardin, D. Dissociated response in metastatic cancer: an atypical pattern brought into the spotlight with immunotherapy. Front. Oncol. 10, 566297 (2020).
pubmed: 33072599
pmcid: 7531255
doi: 10.3389/fonc.2020.566297
Litiere, S. et al. RECIST 1.1 for response evaluation apply not only to chemotherapy-treated patients but also to targeted cancer agents: a pooled database analysis. J. Clin. Oncol. 37, 1102–1110 (2019).
pubmed: 30860949
pmcid: 6494357
doi: 10.1200/JCO.18.01100
Qin, K., Hou, H., Liang, Y. & Zhang, X. Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis. BMC Cancer 20, 328 (2020).
pubmed: 32299384
pmcid: 7164297
doi: 10.1186/s12885-020-06805-5
Vokes, N. I. et al. Concurrent TP53 mutations facilitate resistance evolution in EGFR-mutant lung adenocarcinoma. J. Thorac. Oncol. 17, 779–792 (2022).
pubmed: 35331964
pmcid: 10478031
doi: 10.1016/j.jtho.2022.02.011
Bielski, C. M. et al. Genome doubling shapes the evolution and prognosis of advanced cancers. Nat. Genet. 50, 1189–1195 (2018).
pubmed: 30013179
pmcid: 6072608
doi: 10.1038/s41588-018-0165-1
Lopez, S. et al. Interplay between whole-genome doubling and the accumulation of deleterious alterations in cancer evolution. Nat. Genet. 52, 283–293 (2020).
pubmed: 32139907
pmcid: 7116784
doi: 10.1038/s41588-020-0584-7
Sun, H. et al. Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidatesfor targeted treatment. Nat. Commun. 12, 5086 (2021).
pubmed: 34429404
pmcid: 8384880
doi: 10.1038/s41467-021-25177-3
Watkins, T. B. K. et al. Pervasive chromosomal instability and karyotype order in tumour evolution. Nature 587, 126–132 (2020).
pubmed: 32879494
pmcid: 7611706
doi: 10.1038/s41586-020-2698-6
Dewhurst, S. M. et al. Tolerance of whole-genome doubling propagates chromosomal instability and accelerates cancer genome evolution. Cancer Discov. 4, 175–185 (2014).
pubmed: 24436049
pmcid: 4293454
doi: 10.1158/2159-8290.CD-13-0285
Dentro, S. C. et al. Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes. Cell 184, 2239–2254.e2239 (2021).
pubmed: 33831375
pmcid: 8054914
doi: 10.1016/j.cell.2021.03.009
Jamal-Hanjani, M. et al. Tracking the evolution of non-small-cell lung cancer. N. Engl. J. Med. 376, 2109–2121 (2017).
pubmed: 28445112
doi: 10.1056/NEJMoa1616288
Weiss, M. B. et al. Deletion of p53 in human mammary epithelial cells causes chromosomal instability and altered therapeutic response. Oncogene 29, 4715–4724 (2010).
pubmed: 20562907
pmcid: 3164558
doi: 10.1038/onc.2010.220
Kuznetsova, A. Y. et al. Chromosomal instability, tolerance of mitotic errors and multidrug resistance are promoted by tetraploidization in human cells. Cell Cycle 14, 2810–2820 (2015).
pubmed: 26151317
pmcid: 4614355
doi: 10.1080/15384101.2015.1068482
Donehower, L. A. et al. Integrated analysis of TP53 gene and pathway alterations in the cancer genome atlas. Cell Rep. 28, 1370–1384.e1375 (2019).
pubmed: 31365877
pmcid: 7546539
doi: 10.1016/j.celrep.2019.07.001
Ganem, N. J. et al. Cytokinesis failure triggers hippo tumor suppressor pathway activation. Cell 158, 833–848 (2014).
pubmed: 25126788
pmcid: 4136486
doi: 10.1016/j.cell.2014.06.029
Frankell, A. M. et al. The evolution of lung cancer and impact of subclonal selection in TRACERx. Nature 616, 525–533 (2023).
Chen, J. et al. Genomic landscape of lung adenocarcinoma in East Asians. Nat. Genet. 52, 177–186 (2020).
Shepherd, F. A. et al. Pooled analysis of the prognostic and predictive effects of TP53 comutation status combined with KRAS or EGFR mutation in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy. J. Clin. Oncol. 35, 2018–2027 (2017).
pubmed: 28453411
pmcid: 6075828
doi: 10.1200/JCO.2016.71.2893
Sos, M. L. et al. PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. Cancer Res. 69, 3256–3261 (2009).
pubmed: 19351834
pmcid: 2849653
doi: 10.1158/0008-5472.CAN-08-4055
Politi, K., Fan, P. D., Shen, R., Zakowski, M. & Varmus, H. Erlotinib resistance in mouse models of epidermal growth factor receptor-induced lung adenocarcinoma. Dis. Model Mech. 3, 111–119, (2010).
pubmed: 20007486
doi: 10.1242/dmm.003681
Sequist, L. V. et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci. Transl. Med. 3, 75ra26 (2011).
pubmed: 21430269
pmcid: 3132801
doi: 10.1126/scitranslmed.3002003
Oser, M. G., Niederst, M. J., Sequist, L. V. & Engelman, J. A. Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. Lancet Oncol. 16, e165–172, (2015).
pubmed: 25846096
pmcid: 4470698
doi: 10.1016/S1470-2045(14)71180-5
Li, Y., Mangasarian, K., Mansukhani, A. & Basilico, C. Activation of FGF receptors by mutations in the transmembrane domain. Oncogene 14, 1397–1406 (1997).
pubmed: 9136983
doi: 10.1038/sj.onc.1200983
Laks, E. et al. Clonal decomposition and DNA replication states defined by scaled single-cell genome sequencing. Cell 179, 1207–1221.e1222 (2019).
pubmed: 31730858
pmcid: 6912164
doi: 10.1016/j.cell.2019.10.026
Morgillo, F., Della Corte, C. M., Fasano, M. & Ciardiello, F. Mechanisms of resistance to EGFR-targeted drugs: lung cancer. ESMO Open 1, e000060 (2016).
pubmed: 27843613
pmcid: 5070275
doi: 10.1136/esmoopen-2016-000060
Endesfelder, D. et al. Chromosomal instability selects gene copy-number variants encoding core regulators of proliferation in ER+ breast cancer. Cancer Res. 74, 4853–4863 (2014).
pubmed: 24970479
pmcid: 4167338
doi: 10.1158/0008-5472.CAN-13-2664
Chin, T. M. et al. Reduced Erlotinib sensitivity of epidermal growth factor receptor-mutant non-small cell lung cancer following cisplatin exposure: a cell culture model of second-line erlotinib treatment. Clin. Cancer Res. 14, 6867–6876 (2008).
pubmed: 18980981
pmcid: 2710881
doi: 10.1158/1078-0432.CCR-08-0093
Ramirez, M. et al. Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells. Nat. Commun. 7, 10690 (2016).
pubmed: 26891683
pmcid: 4762880
doi: 10.1038/ncomms10690
Ruiz, C. et al. Single-molecule detection of cancer mutations using a novel PCR-LDR-qPCR assay. Hum. Mutat. 41, 1051–1068 (2020).
de Anta, J. M. et al. TP53 mutational pattern in Spanish and Polish non-small cell lung cancer patients: null mutations are associated with poor prognosis. Oncogene 15, 2951–2958 (1997).
pubmed: 9416838
doi: 10.1038/sj.onc.1201475
Newcomb, R., Dean, E., McKinney, B. J. & Alvarez, J. V. Context-dependent effects of whole-genome duplication during mammary tumor recurrence. Sci. Rep. 11, 14932 (2021).
pubmed: 34294755
pmcid: 8298634
doi: 10.1038/s41598-021-94332-z
Hata, A. N. et al. Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition. Nat. Med. 22, 262–269 (2016).
pubmed: 26828195
pmcid: 4900892
doi: 10.1038/nm.4040
Torigoe, H. et al. Therapeutic strategies for afatinib-resistant lung cancer harboring HER2 alterations. Cancer Sci. 109, 1493–1502 (2018).
pubmed: 29532558
pmcid: 5980184
doi: 10.1111/cas.13571
Goyal, Y. et al. Diverse clonal fates emerge upon drug treatment of homogeneous cancer cells. Nature 620, 651–659 (2023).
Hieronymus, H. et al. Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death. Elife https://doi.org/10.7554/eLife.37294 (2018).
Akhavan, D. et al. De-repression of PDGFRbeta transcription promotes acquired resistance to EGFR tyrosine kinase inhibitors in glioblastoma patients. Cancer Discov. 3, 534–547 (2013).
pubmed: 23533263
pmcid: 3651754
doi: 10.1158/2159-8290.CD-12-0502
Politi, K. et al. Lung adenocarcinomas induced in mice by mutant EGF receptors found in human lung cancers respond to a tyrosine kinase inhibitor or to down-regulation of the receptors. Genes Dev. 20, 1496–1510 (2006).
pubmed: 16705038
pmcid: 1475762
doi: 10.1101/gad.1417406
Wang, L. et al. Restricted expression of mutant SOD1 in spinal motor neurons and interneurons induces motor neuron pathology. Neurobiol. Dis. 29, 400–408 (2008).
pubmed: 18054242
doi: 10.1016/j.nbd.2007.10.004
Marino, S., Vooijs, M., van Der Gulden, H., Jonkers, J. & Berns, A. Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Genes Dev. 14, 994–1004 (2000).
pubmed: 10783170
pmcid: 316543
doi: 10.1101/gad.14.8.994
Jackson, E. L. et al. The differential effects of mutant p53 alleles on advanced murine lung cancer. Cancer Res. 65, 10280–10288 (2005).
pubmed: 16288016
doi: 10.1158/0008-5472.CAN-05-2193
Dunn, J. M. et al. Image cytometry accurately detects DNA ploidy abnormalities and predicts late relapse to high-grade dysplasia and adenocarcinoma in Barrett’s oesophagus following photodynamic therapy. Br. J. Cancer 102, 1608–1617 (2010).
pubmed: 20461081
pmcid: 2883155
doi: 10.1038/sj.bjc.6605688
Koboldt, D. C. et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 22, 568–576 (2012).
pubmed: 22300766
pmcid: 3290792
doi: 10.1101/gr.129684.111
Cibulskis, K. et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat. Biotechnol. 31, 213–219 (2013).
pubmed: 23396013
pmcid: 3833702
doi: 10.1038/nbt.2514
Fang, H. et al. Indel variant analysis of short-read sequencing data with Scalpel. Nat. Protoc. 11, 2529–2548 (2016).
pubmed: 27854363
pmcid: 5507611
doi: 10.1038/nprot.2016.150
Wang, K. et al. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).
McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303, (2010).
pubmed: 20644199
pmcid: 2928508
doi: 10.1101/gr.107524.110
Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–1760 (2009).
pubmed: 19451168
pmcid: 2705234
doi: 10.1093/bioinformatics/btp324
Gerstung, M. et al. Reliable detection of subclonal single-nucleotide variants in tumour cell populations. Nat. Commun. 3, 811 (2012).
pubmed: 22549840
doi: 10.1038/ncomms1814
Lee, J. et al. Synteny Portal: a web-based application portal for synteny block analysis. Nucleic Acids Res. 44, W35–40, (2016).
pubmed: 27154270
pmcid: 4987893
doi: 10.1093/nar/gkw310
Bakker, B. et al. Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies. Genome Biol. 17, 115 (2016).
pubmed: 27246460
pmcid: 4888588
doi: 10.1186/s13059-016-0971-7
van den Bos, H. et al. Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer’s disease neurons. Genome Biol. 17, 116 (2016).
pubmed: 27246599
pmcid: 4888403
doi: 10.1186/s13059-016-0976-2
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
pubmed: 22388286
pmcid: 3322381
doi: 10.1038/nmeth.1923
Jun, G., Wing, M. K., Abecasis, G. R. & Kang, H. M. An efficient and scalable analysis framework for variant extraction and refinement from population-scale DNA sequence data. Genome Res. 25, 918–925 (2015).
pubmed: 25883319
pmcid: 4448687
doi: 10.1101/gr.176552.114
Sondka, Z. et al. The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers. Nat. Rev. Cancer 18, 696–705 (2018).
pubmed: 30293088
pmcid: 6450507
doi: 10.1038/s41568-018-0060-1
Bailey, M. H. et al. Comprehensive characterization of cancer driver genes and mutations. Cell 173, 371–385 e318 (2018).
pubmed: 29625053
pmcid: 6029450
doi: 10.1016/j.cell.2018.02.060
RCoreTeam. R: a language and environment for statistical computing (2018).
Hobor, S. et al. Single-cell mouse and PC9 data for “Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling”. GitHub https://doi.org/10.5281/zenodo.10658423 (2024).