IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-27341-1.html
   My bibliography  Save this article

The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics

Author

Listed:
  • Ming Tang

    (The University of Texas MD Anderson Cancer Center)

  • Hussein A. Abbas

    (The University of Texas MD Anderson Cancer Center)

  • Marcelo V. Negrao

    (The University of Texas MD Anderson Cancer Center)

  • Maheshwari Ramineni

    (Baylor College of Medicine)

  • Xin Hu

    (The University of Texas MD Anderson Cancer Center)

  • Shawna Marie Hubert

    (The University of Texas MD Anderson Cancer Center)

  • Junya Fujimoto

    (The University of Texas MD Anderson Cancer Center)

  • Alexandre Reuben

    (The University of Texas MD Anderson Cancer Center)

  • Susan Varghese

    (The University of Texas MD Anderson Cancer Center)

  • Jianhua Zhang

    (The University of Texas MD Anderson Cancer Center)

  • Jun Li

    (The University of Texas MD Anderson Cancer Center)

  • Chi-Wan Chow

    (The University of Texas MD Anderson Cancer Center)

  • Xizeng Mao

    (The University of Texas MD Anderson Cancer Center)

  • Xingzhi Song

    (The University of Texas MD Anderson Cancer Center)

  • Won-Chul Lee

    (The University of Texas MD Anderson Cancer Center)

  • Jia Wu

    (The University of Texas MD Anderson Cancer Center)

  • Latasha Little

    (The University of Texas MD Anderson Cancer Center)

  • Curtis Gumbs

    (The University of Texas MD Anderson Cancer Center)

  • Carmen Behrens

    (The University of Texas MD Anderson Cancer Center)

  • Cesar Moran

    (The University of Texas MD Anderson Cancer Center)

  • Annikka Weissferdt

    (The University of Texas MD Anderson Cancer Center)

  • J. Jack Lee

    (The University of Texas MD Anderson Cancer Center)

  • Boris Sepesi

    (The University of Texas MD Anderson Cancer Center)

  • Stephen Swisher

    (The University of Texas MD Anderson Cancer Center)

  • Chao Cheng

    (Baylor College of Medicine)

  • Jonathan Kurie

    (The University of Texas MD Anderson Cancer Center)

  • Don Gibbons

    (The University of Texas MD Anderson Cancer Center)

  • John V. Heymach

    (The University of Texas MD Anderson Cancer Center)

  • Ignacio I. Wistuba

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • P. Andrew Futreal

    (The University of Texas MD Anderson Cancer Center)

  • Neda Kalhor

    (The University of Texas MD Anderson Cancer Center)

  • Jianjun Zhang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

Abstract

Histology plays an essential role in therapeutic decision-making for lung cancer patients. However, the molecular determinants of lung cancer histology are largely unknown. We conduct whole-exome sequencing and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes from 9 patients with lung cancers of mixed histology. A median of 68.9% of point mutations and 83% of copy number aberrations are shared between different histologic components within the same tumors. Furthermore, different histologic components within the tumors demonstrate similar subclonal architecture. On the other hand, transcriptomic profiling reveals shared pathways between the same histologic subtypes from different patients, which is supported by the analyses of the transcriptomic data from 141 cell lines and 343 lung cancers of different histologic subtypes. These data derived from mixed histologic subtypes in the setting of identical genetic background and exposure history support that the histologic fate of lung cancer cells is associated with transcriptomic features rather than the genomic profiles in most tumors.

Suggested Citation

  • Ming Tang & Hussein A. Abbas & Marcelo V. Negrao & Maheshwari Ramineni & Xin Hu & Shawna Marie Hubert & Junya Fujimoto & Alexandre Reuben & Susan Varghese & Jianhua Zhang & Jun Li & Chi-Wan Chow & Xiz, 2021. "The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27341-1
    DOI: 10.1038/s41467-021-27341-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27341-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-27341-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jordi Barretina & Giordano Caponigro & Nicolas Stransky & Kavitha Venkatesan & Adam A. Margolin & Sungjoon Kim & Christopher J.Wilson & Joseph Lehár & Gregory V. Kryukov & Dmitriy Sonkin & Anupama Red, 2012. "Addendum: The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity," Nature, Nature, vol. 492(7428), pages 290-290, December.
    2. Jordi Barretina & Giordano Caponigro & Nicolas Stransky & Kavitha Venkatesan & Adam A. Margolin & Sungjoon Kim & Christopher J. Wilson & Joseph Lehár & Gregory V. Kryukov & Dmitriy Sonkin & Anupama Re, 2012. "The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity," Nature, Nature, vol. 483(7391), pages 603-607, March.
    3. Yu Liu & Jianjun Zhang & Lin Li & Guangliang Yin & Jianhua Zhang & Shan Zheng & Hannah Cheung & Ning Wu & Ning Lu & Xizeng Mao & Longhai Yang & Jiexin Zhang & Li Zhang & Sahil Seth & Huang Chen & Xing, 2016. "Genomic heterogeneity of multiple synchronous lung cancer," Nature Communications, Nature, vol. 7(1), pages 1-8, December.
    4. Ludmil B. Alexandrov & Serena Nik-Zainal & David C. Wedge & Samuel A. J. R. Aparicio & Sam Behjati & Andrew V. Biankin & Graham R. Bignell & Niccolò Bolli & Ake Borg & Anne-Lise Børresen-Dale & Sandri, 2013. "Correction: Corrigendum: Signatures of mutational processes in human cancer," Nature, Nature, vol. 502(7470), pages 258-258, October.
    5. Floris P. Barthel & Kevin C. Johnson & Frederick S. Varn & Anzhela D. Moskalik & Georgette Tanner & Emre Kocakavuk & Kevin J. Anderson & Olajide Abiola & Kenneth Aldape & Kristin D. Alfaro & Donat Alp, 2019. "Longitudinal molecular trajectories of diffuse glioma in adults," Nature, Nature, vol. 576(7785), pages 112-120, December.
    6. Matthew J. Niederst & Lecia V. Sequist & John T. Poirier & Craig H. Mermel & Elizabeth L. Lockerman & Angel R. Garcia & Ryohei Katayama & Carlotta Costa & Kenneth N. Ross & Teresa Moran & Emily Howe &, 2015. "RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    7. Xin Hu & Junya Fujimoto & Lisha Ying & Junya Fukuoka & Kazuto Ashizawa & Wenyong Sun & Alexandre Reuben & Chi-Wan Chow & Nicholas McGranahan & Runzhe Chen & Jinlin Hu & Myrna C. Godoy & Kazuhiro Tabat, 2019. "Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    8. Ludmil B. Alexandrov & Serena Nik-Zainal & David C. Wedge & Samuel A. J. R. Aparicio & Sam Behjati & Andrew V. Biankin & Graham R. Bignell & Niccolò Bolli & Ake Borg & Anne-Lise Børresen-Dale & Sandri, 2013. "Signatures of mutational processes in human cancer," Nature, Nature, vol. 500(7463), pages 415-421, August.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jurica Levatić & Marina Salvadores & Francisco Fuster-Tormo & Fran Supek, 2022. "Mutational signatures are markers of drug sensitivity of cancer cells," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Xing Cheng & Jing An & Jitong Lou & Qisheng Gu & Weimin Ding & Gaith Nabil Droby & Yilin Wang & Chenghao Wang & Yanzhe Gao & Jay Ramanlal Anand & Abigail Shelton & Andrew Benson Satterlee & Breanna Ma, 2024. "Trans-lesion synthesis and mismatch repair pathway crosstalk defines chemoresistance and hypermutation mechanisms in glioblastoma," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Wenying Peng & Bin Li & Jin Li & Lianpeng Chang & Jing Bai & Yuting Yi & Rongrong Chen & Yanyan Zhang & Chen Chen & Xingxiang Pu & Meilin Jiang & Jia Li & Rui Zhong & Fang Xu & Bolin Chen & Li Xu & Ni, 2022. "Clinical and genomic features of Chinese lung cancer patients with germline mutations," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Ming Chen & Runzhe Chen & Ying Jin & Jun Li & Xin Hu & Jiexin Zhang & Junya Fujimoto & Shawna M. Hubert & Carl M. Gay & Bo Zhu & Yanhua Tian & Nicholas McGranahan & Won-Chul Lee & Julie George & Xiao , 2021. "Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    5. Michelle Dietzen & Haoran Zhai & Olivia Lucas & Oriol Pich & Christopher Barrington & Wei-Ting Lu & Sophia Ward & Yanping Guo & Robert E. Hynds & Simone Zaccaria & Charles Swanton & Nicholas McGranaha, 2024. "Replication timing alterations are associated with mutation acquisition during breast and lung cancer evolution," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    6. Anna Luiza Silva Almeida Vicente & Alexei Novoloaca & Vincent Cahais & Zainab Awada & Cyrille Cuenin & Natália Spitz & André Lopes Carvalho & Adriane Feijó Evangelista & Camila Souza Crovador & Rui Ma, 2022. "Cutaneous and acral melanoma cross-OMICs reveals prognostic cancer drivers associated with pathobiology and ultraviolet exposure," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Teresa Maria Rosaria Noviello & Anna Maria Giacomo & Francesca Pia Caruso & Alessia Covre & Roberta Mortarini & Giovanni Scala & Maria Claudia Costa & Sandra Coral & Wolf H. Fridman & Catherine Sautès, 2023. "Guadecitabine plus ipilimumab in unresectable melanoma: five-year follow-up and integrated multi-omic analysis in the phase 1b NIBIT-M4 trial," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Qi Zhao & Feng Wang & Yan-Xing Chen & Shifu Chen & Yi-Chen Yao & Zhao-Lei Zeng & Teng-Jia Jiang & Ying-Nan Wang & Chen-Yi Wu & Ying Jing & You-Sheng Huang & Jing Zhang & Zi-Xian Wang & Ming-Ming He & , 2022. "Comprehensive profiling of 1015 patients’ exomes reveals genomic-clinical associations in colorectal cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    9. Seungyeul Yoo & Abhilasha Sinha & Dawei Yang & Nasser K. Altorki & Radhika Tandon & Wenhui Wang & Deebly Chavez & Eunjee Lee & Ayushi S. Patel & Takashi Sato & Ranran Kong & Bisen Ding & Eric E. Schad, 2022. "Integrative network analysis of early-stage lung adenocarcinoma identifies aurora kinase inhibition as interceptor of invasion and progression," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    10. Alon Stern & Mariam Fokra & Boris Sarvin & Ahmad Abed Alrahem & Won Dong Lee & Elina Aizenshtein & Nikita Sarvin & Tomer Shlomi, 2023. "Inferring mitochondrial and cytosolic metabolism by coupling isotope tracing and deconvolution," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. Rebecca J. Austin & Jasmin Straube & Rohit Halder & Yashaswini Janardhanan & Claudia Bruedigam & Matthew Witkowski & Leanne Cooper & Amy Porter & Matthias Braun & Fernando Souza-Fonseca-Guimaraes & Si, 2023. "Oncogenic drivers dictate immune control of acute myeloid leukemia," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    12. Yanli Liu & Zhong Wu & Jin Zhou & Dinesh K. A. Ramadurai & Katelyn L. Mortenson & Estrella Aguilera-Jimenez & Yifei Yan & Xiaojun Yang & Alison M. Taylor & Katherine E. Varley & Jason Gertz & Peter S., 2021. "A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    13. Sayantani Ghosh Dastidar & Bony Kumar & Bo Lauckner & Damien Parrello & Danielle Perley & Maria Vlasenok & Antariksh Tyagi & Nii Koney-Kwaku Koney & Ata Abbas & Sergei Nechaev, 2023. "Transcriptional responses of cancer cells to heat shock-inducing stimuli involve amplification of robust HSF1 binding," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    14. Sumana Srivatsa & Hesam Montazeri & Gaia Bianco & Mairene Coto-Llerena & Mattia Marinucci & Charlotte K. Y. Ng & Salvatore Piscuoglio & Niko Beerenwinkel, 2022. "Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    15. Cemal Erdem & Sean M. Gross & Laura M. Heiser & Marc R. Birtwistle, 2023. "MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    16. David Wang & Mathieu Quesnel-Vallieres & San Jewell & Moein Elzubeir & Kristen Lynch & Andrei Thomas-Tikhonenko & Yoseph Barash, 2023. "A Bayesian model for unsupervised detection of RNA splicing based subtypes in cancers," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    17. Lisa Veghini & Davide Pasini & Rui Fang & Pietro Delfino & Dea Filippini & Christian Neander & Caterina Vicentini & Elena Fiorini & Francesca Lupo & Sabrina L. D’Agosto & Carmine Carbone & Antonio Ago, 2024. "Differential activity of MAPK signalling defines fibroblast subtypes in pancreatic cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    18. Ezra Y. Rosen & Helen H. Won & Youyun Zheng & Emiliano Cocco & Duygu Selcuklu & Yixiao Gong & Noah D. Friedman & Ino Bruijn & Onur Sumer & Craig M. Bielski & Casey Savin & Caitlin Bourque & Christina , 2022. "The evolution of RET inhibitor resistance in RET-driven lung and thyroid cancers," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    19. Yonina R. Murciano-Goroff & Alison M. Schram & Ezra Y. Rosen & Helen Won & Yixiao Gong & Anne Marie Noronha & Yelena Y. Janjigian & Zsofia K. Stadler & Jason C. Chang & Soo-Ryum Yang & Diana Mandelker, 2022. "Reversion mutations in germline BRCA1/2-mutant tumors reveal a BRCA-mediated phenotype in non-canonical histologies," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    20. Saptarshi Chakraborty & Colin B. Begg & Ronglai Shen, 2021. "Using the “Hidden” genome to improve classification of cancer types," Biometrics, The International Biometric Society, vol. 77(4), pages 1445-1455, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27341-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.