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K. Shiraishi
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-035 - Mutational Signatures and Their Association with Clinicopathological Features in Lung Adenocarcinoma of Smokers (ID 8623)
09:30 - 09:30 | Author(s): K. Shiraishi
- Abstract
Background:
Lung adenocarcinoma (LADC) harboring druggable driver oncogene such as EGFR mutation and ALK fusion can be treated with molecular-targeted drugs. These oncogene aberrations are frequently observed in LADCs of never-smoker, while LADCs of smokers often lack such druggable oncogene aberrations. Therefore, understanding mutation profile of LADCs of smokers is required to improve precision lung cancer medicine..
Method:
We analyzed mutational signatures of somatic mutations in 373 LADCs (smoker 220 cases; 59%, never-smoker 153 cases; 31%) of Japanese using whole exome sequencing data. Four mutational signatures were identified by non-negative matrix factorization and logistic regression analysis. We are now analyzing significantly mutated gene (SMG)s by MutSigCV1.5 of LADCs of smokers and associations of each signature with clinicopathological factors including histological subtype and prognosis.
Result:
Indel mutations as well as well-characterized C>A mutations were defined as mutational event more prevalent in LADC of ever-smokers than in never-smokers (P=8.76E-15 and P=0.000417 respectively). A novel set of genes were identified as a main target for indel mutations (7.4%; 22 of 296 samples), and their mutations were significantly associated with smoking and with UIP co-occurrence in their lung (P=0.0068 and P=0.037, respectively). Indel mutations in 3’-UTRs of these genes caused specific reduction in mutant transcripts, while those in coding region caused truncation of polypeptide.
Conclusion:
A novel gene set including those in 3’-UTR, would contribute to LADC development in smokers and associated with usual interstitial pneumonia, by promoting undifferentiation of tumor cells.
