Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma

Xing Hua, Wei Zhao, Angela C. Pesatori, Dario Consonni, Neil E. Caporaso, Tongwu Zhang, Bin Zhu, Mingyi Wang, Kristine Jones, Belynda Hicks, Lei Song, Joshua Sampson, David C. Wedge, Jianxin Shi and Maria Teresa Landi ()
Additional contact information
Xing Hua: DHHS
Wei Zhao: DHHS
Angela C. Pesatori: University of Milan
Dario Consonni: Occupational Health Unit
Neil E. Caporaso: National Cancer Institute, NIH, DHHS
Tongwu Zhang: DHHS
Bin Zhu: DHHS
Mingyi Wang: Leidos Biomedical Research Inc.
Kristine Jones: Leidos Biomedical Research Inc.
Belynda Hicks: Leidos Biomedical Research Inc.
Lei Song: Leidos Biomedical Research Inc.
Joshua Sampson: DHHS
David C. Wedge: Big Data Institute
Jianxin Shi: DHHS
Maria Teresa Landi: DHHS

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract Intratumor heterogeneity (ITH) of genomic alterations may impact prognosis of lung adenocarcinoma (LUAD). Here, we investigate ITH of somatic copy number alterations (SCNAs), DNA methylation, and point mutations in lung cancer driver genes in 292 tumor samples from 84 patients with LUAD. LUAD samples show substantial SCNA and methylation ITH, and clonal architecture analyses present congruent evolutionary trajectories for SCNAs and DNA methylation aberrations. Methylation ITH mapping to gene promoter areas or tumor suppressor genes is low. Moreover, ITH composed of genetic and epigenetic mechanisms altering the same cancer driver genes is shown in several tumors. To quantify ITH for valid statistical association analyses, we develope an average pairwise ITH index (APITH), which does not depend on the number of samples per tumor. Both APITH indexes for SCNAs and methylation aberrations show significant associations with poor prognosis. This study further establishes the important clinical implications of genetic and epigenetic ITH in LUAD.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16295-5

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DOI: 10.1038/s41467-020-16295-5

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