Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing
Open accessAbstract
Cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed intratumor heterogeneity (ITH). ITH in lung cancers has not been well studied. We applied multiregion whole-exome sequencing (WES) on 11 localized lung adenocarcinomas. All tumors showed clear evidence of ITH. On average, 76% of all mutations and 20 out of 21 known cancer gene mutations were identified in all regions of individual tumors, which suggested that single-region sequencing may be adequate to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. With a median follow-up of 21 months after surgery, three patients have relapsed, and all three patients had significantly larger fractions of subclonal mutations in their primary tumors than patients without relapse. These data indicate that a larger subclonal mutation fraction may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas.
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There is evidence that APOBEC-mediated mutagenesis fuels sub-clonal diversification and branched evolution.
“While the full extent to which mutational processes account for unique combinations of somatic genomic alterations in NSCLC is currently unknown, there is evidence that APOBEC-mediated mutagenesis fuels sub-clonal diversification and branched evolution78, 79.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [78]
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- Authors
- Zhang, J., Fujimoto, J., Zhang, J., Wedge, D. C., Song, X., Zhang, J., Seth, S., Chow, C.-W., Cao, Y., Gumbs, C., Gold, K. A., Kalhor, N., Little, L., Mahadeshwar, H., Moran, C., Protopopov, A., Sun, H., Tang, J., Wu, X., Ye, Y., William, W. N., Lee, J. J., Heymach, J. V., Hong, W. K., Swisher, S., Wistuba, I. I., & Futreal, P. A.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Wellcome Sanger Institute (GB)
- Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
- Corresponding author
- Futreal, P. Andrew
- ORCID
- Venue
- Science
- Published
- 2014-10-10
- Volume
- 346
- Issue
- 6206
- Pages
- 256-259
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4354858
- OpenAlex
- W2038268416
- Cited by
- 965
- References
- 46
- Citations by year
- 2026: 17 · 2025: 32 · 2024: 51 · 2023: 66 · 2022: 77 · 2021: 92 · 2020: 94 · 2019: 85 · 2018: 108 · 2017: 113 · 2016: 119 · 2015: 102 · 2014: 8
- FWCI
- 36.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- National Cancer Institute (CA 016672, (P50-CA70907, T32CA009666, P50CA070907, P30CA016672)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- intratumoral heterogeneity, lung adenocarcinoma, localized lung cancer, exome sequencing, subclonal mutations, cancer mutations, tumor recurrence, postoperative recurrence
- MeSH terms
- Adenocarcinoma of Lung, Adenocarcinoma, DNA Mutational Analysis, Humans, Lung Neoplasms, Mutation, Neoplasm Recurrence, Local, Genetic Heterogeneity, Genes, Neoplasm, Exome
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