The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
The transcriptional landscape and mutational profile of lung adenocarcinoma
Open accessAbstract
All cancers harbor molecular alterations in their genomes. The transcriptional consequences of these somatic mutations have not yet been comprehensively explored in lung cancer. Here we present the first large scale RNA sequencing study of lung adenocarcinoma, demonstrating its power to identify somatic point mutations as well as transcriptional variants such as gene fusions, alternative splicing events, and expression outliers. Our results reveal the genetic basis of 200 lung adenocarcinomas in Koreans including deep characterization of 87 surgical specimens by transcriptome sequencing. We identified driver somatic mutations in cancer genes including EGFR, KRAS, NRAS, BRAF, PIK3CA, MET, and CTNNB1. Candidates for novel driver mutations were also identified in genes newly implicated in lung adenocarcinoma such as LMTK2, ARID1A, NOTCH2, and SMARCA4. We found 45 fusion genes, eight of which were chimeric tyrosine kinases involving ALK, RET, ROS1, FGFR2, AXL, and PDGFRA. Among 17 recurrent alternative splicing events, we identified exon 14 skipping in the proto-oncogene MET as highly likely to be a cancer driver. The number of somatic mutations and expression outliers varied markedly between individual cancers and was strongly correlated with smoking history of patients. We identified genomic blocks within which gene expression levels were consistently increased or decreased that could be explained by copy number alterations in samples. We also found an association between lymph node metastasis and somatic mutations in TP53. These findings broaden our understanding of lung adenocarcinoma and may also lead to new diagnostic and therapeutic approaches.
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BackgroundThe protein kinase complement of the human genome
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Cited by
Signatures of mutational processes in human cancer
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Comprehensive molecular profiling of lung adenocarcinoma
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ERK/MAPK signalling pathway and tumorigenesis (Review)
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Metadata
- Authors
- Seo, J.-S., Ju, Y. S., Lee, W.-C., Shin, J.-Y., Lee, J. K., Bleazard, T., Lee, J., Jung, Y. J., Kim, J.-O., Shin, J.-Y., Yu, S.-B., Kim, J., Lee, E.-R., Kang, C.-H., Park, I.-K., Rhee, H., Lee, S.-H., Kim, J.-I., Kang, J.-H., & Kim, Y. T.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-09-13
- Volume
- 22
- Issue
- 11
- Pages
- 2109-2119
- ISSN
- 1088-9051 (ISSN-L)
- OpenAlex
- W2071480068
- Cited by
- 584
- References
- 51
- Type
- posted content
- Language
- en
- Open access
- bronze
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- Seo, J.-S., Ju, Y. S., Lee, W.-C., Shin, J.-Y., Lee, J. K., Bleazard, T., Lee, J., Jung, Y. J., Kim, J.-O., Shin, J.-Y., Yu, S.-B., Kim, J., Lee, E.-R., Kang, C.-H., Park, I.-K., Rhee, H., Lee, S.-H., Kim, J.-I., Kang, J.-H., & Kim, Y. T. (2012). The transcriptional landscape and mutational profile of lung adenocarcinoma. Genome Research. https://doi.org/10.1101/gr.145144.112
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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