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S.B. Lee
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MINI 08 - Prognostic/Predictive Biomarkers (ID 106)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:T.E. Stinchcombe, N. Pavlakis
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 4a-4f
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MINI08.11 - Genome-Wide Association Analysis Identifies Novel Genetic Determinants of Cancer Metastasis in Korean Lung Adenocarcinoma (ID 2363)
17:50 - 17:55 | Author(s): S.B. Lee
- Abstract
- Presentation
Background:
Non-small cell lung cancer (NSCLC) is characterized by poor prognosis, and few molecular markers were proven to be associated with cancer metastasis. The aim of the study is to identify the associations between single-nucleotide polymorphisms (SNPs) and distant metastasis of adenocarcinoma of the lung in Korean population.
Methods:
We conducted a genome-wide association study (GWAS) of in 499 Korean lung adenocarcinomas comparing 4,653,588 SNPs genotypes. Analyses were performed to investigate the association between the germline variations in all genes and cancer metastasis, survival and cancer recurrence.
Results:
We undertook a gene-metastasis interaction analysis in a GWAS of lung cancer using a case-control study. (18cases and 481controls) The combined analyses identified two susceptibility loci for metastasis risk in lung adenocarcinoma: SYNE1 [rs117050208, p-value = 1.91 x 10[-14], odds ratio (OR) = 87] and QSOX1 (rs148150589, p-value = 4.46 x 10[-9], OR = 56.5). SYNE1 was known to play crucial roles in the dynamics of genetic progression in colorectal adenocarcinoma and QSOXI was considered a prognostic indicator of metastatic potential in the breast cancer. (Figure1) However, no significant association was found between SNPs and either survival or recurrence. Figure 1
Conclusion:
Our data suggest that the SYNE1 rs117050208 and the QSOX1 rs148150589 may serve as potential biomarkers to influence cancer metastasis in the Korean lung adenocarcinoma. The analysis of the rs117050208 and rs148150589 polymorphism can help identify patients at high risk of distant metastasis of lung adenocarcinoma.
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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
- Moderators:Y. Koh, R.K. Thomas
- Coordinates: 9/08/2015, 10:45 - 12:15, 205+207
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MINI13.07 - Kinome Targeted Deep Sequencing Identifies Novel Mutations in Korean Adenocarcinoma of the Lung (ID 1421)
11:20 - 11:25 | Author(s): S.B. Lee
- Abstract
- Presentation
Background:
Various protein kinases have been discovered as drivers in cancer and subsequently used as therapeutic targets.
Methods:
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.
Results:
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
Conclusion:
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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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-029 - Development of Lung Cancer Diagnosis Panel Based on the Target Sequencing Technology: A Validation Result (ID 1489)
09:30 - 09:30 | Author(s): S.B. Lee
- Abstract
Background:
Recent development of next generation sequencing technologies enabled the accumulation of a lot of information about genomic variants in cancer. However, the price of whole genome / exome sequencing is still high to be used as a diagnostic testing for treatment decision-making.
Methods:
To develop a clinically useful diagnostic kit, we designed a lung cancer diagnostics (LCDx) panel to discover all coding mutations on 42 genes, MET exon14 skipping and fusion genes involving 4 genes (ALK, RET, ROS1 and AXL). The performance of the panel was tested by using 100 lung cancer tissues and compared the results to those of three different diagnostic platforms, including Sanger sequencing, Ion AmpliSeq Cancer Hotspot Panel (Thermo-Life Technologies) and fluorescence in situ hybridization (FISH).
Results:
For the detection of EGFR and KRAS mutations, LCDx panel showed 100% sensitivity and specificity. For fusion discovery, the specificity reached 93% but the sensitivity was only 35%, which suggested a novel design of fusion detection method should be addressed for future development.EML4-ALK
FISH+ FISH- LCDx+ 8 8 Sensitivity 42.1% LCDx- 11 62 Specificity 88.6% KIF5B-RET
FISH+ FISH- LCDx+ 1 2 Sensitivity 14.3% LCDx- 6 78 Specificity 97.5%
Conclusion:
In our result, we confirmed all the lung cancer mutations currently being examined by multiple clinical assays could be identified by one target sequencing method more accurately and conveniently using LCDx. Our results suggest that, with improvement of fusion discovery, cancer panel such as our LCDx panel, can be used for clinical diagnostics and treatment decision making of non-small cell lung cancer patients.
