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M. Sugita
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-016 - Minority Exon 19 Deletions Also Have Major Response of EGFR Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer (ID 2658)
09:30 - 09:30 | Author(s): M. Sugita
- Abstract
Background:
This study points out an issue of PCR methods to detect exon 19 deletions. Exon 19 deletions are most important among exon 18 to 21 EGFR mutations to dictate EGFR tyrosine kinase inhibitors (EGFR-TKIs) therapy in non-small cell lung cancer (NSCLC), and exon 19 deletions and insertions have over 170 species by catalog of somatic mutation in cancer (COSMIC). PCR methods are used for clinical examination, because they are useful, rapid and cost-effective to detect EGFR mutations. Some PCR methods could detect all of exon 19 deletions and insertions, while others could not. We investigated the clinical significance of minority exon 19 deletions, which could not be detected according to the PCR methods, selected majority deletions.
Methods:
The study included a series of 73 NSCLC patients, which were treated with EGFR-TKI for recurrent disease after they had undergone surgery from 1992 to 2004. EGFR mutations were detected in 34 (47%) in 73 patients. Sixty patients were evaluable for response, and remaining 13 patients who had taken EGFR-TKI for less than one month. In 60 assessable patients, exon 19 deletions and exon 21 point mutation were detected from 19 patients and 10 patients, respectively. Patients with EGFR mutations had significantly higher response rates to EGFR-TKI than those with wild-type (p=.047), and exon 19 deletions had still rates (p=.024). In 51 samples, including 17 exon 19 deletions and 6 exon 21 mutations, four PCR methods are commonly used in Japan, were performed and compared. PCR-based methods were (1) PCR-Invader for the selected common mutations of exons 18, 19, 20 and 21, and micro capillary electrophoresis for the exhaustive detection of exon 19 deletions and insertions, (2) Peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp for the selected common mutations of exons 18, 19, 20 and 21, and direct sequence for the other mutations, (3) Cycleave PCR for the selected common mutations of exons 18, 20 and 21, and fragment analysis with micro capillary electrophoresis for the exhaustive detection of exon 19 deletions and insertions, (4) Scorpion Amplification Refractory Mutation System (ARMS) for the selected 29 mutations including 19 species of exons 19 deletions and insertions.
Results:
All four methods detected 6 exon 21 mutations as L858R point mutation. However, in exon 19 deletions and insertions including over 170 species, only micro capillary electrophoresis detected all 17 exon 19 deletions. PNA-LNA PCR clamp and direct sequence missed one 9 bp short deletion “L747-E749 del”, which had complete response on EGFR-TKI therapy. Scorpion ARMS missed one 24 bp deletion and insertion “T751-I759 del ins S”, which had stable disease for over 3 years on EGFR-TKI therapy.
Conclusion:
This study suggests micro capillary electrophoresis is necessary for the exhaustive detection of exon 19 deletions and insertions, and may identify tumors responsive to EGFR-TKIs therapy, especially those with small or unusual deletions.
