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MINI 13 - Genetic Alterations and Testing (ID 120)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
MINI13.07 - Kinome Targeted Deep Sequencing Identifies Novel Mutations in Korean Adenocarcinoma of the Lung (ID 1421)
10:45 - 12:15 | Author(s): T.G. Yun
Various protein kinases have been discovered as drivers in cancer and subsequently used as therapeutic targets.
To discover potential target driver genes, we investigated characteristics of genome wide scans of genetic lesions in kinases from 103 Korean lung adenocarcinoma patients, whose driver mutations were unknown or negative after conventional screening of EGFR and KRAS mutations as well as EML4-ALK fusion. We employed targeted, pair-end deep sequencing and screened the coding sequences of 518 protein kinase and genes that are known to be mutated with considerable frequencies in lung adenocarcinoma such as TP53 and EGFR.
Pathway analysis revealed that recurrent alterations were enriched in p53 signaling (TP53, ATM, CHEK2, CDKN2A) and ErbB signaling (EGFR, BRAF, KRAS, ERBB4) pathways. Mutations in TP53 and an EGFR exon 21 hotspot regions were found in 28% (29/103) and 13% (13/103) of cases (Fig 1). TP53 mutation was significantly more common in older group (97%) than in younger group (3%). We identified novel somatic mutations of genes, including CHEK2, NEK2 (mitotic progression) and SMG1 (nonsense-mediated mRNA decay), that have not been highlighted in lung cancer previously. Figure 1 Fig 1. Discovery of recurrent mutations with identical substitutions at the same site
As the inhibitors of these protein kinases can be therapeutic candidates to eradicate cancer cells, our results provide useful information for the development of effective therapeutic target agents, by which the activity of various kinases can be modulated, in adenocarcinoma of the lung.
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