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T. Nishii
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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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MINI13.09 - Next-Generation Sequencing Analysis of Driver Gene Mutations in Pleomorphic Carcinoma of the Lung (ID 1145)
11:30 - 11:35 | Author(s): T. Nishii
- Abstract
- Presentation
Background:
Research into druggable driver gene mutations in non-small cell lung cancer has identified several molecule-targeting agents that are clinically prescribed to inhibit tumor growth in adenocarcinoma. However, lung cancers without targeted driver gene mutations show poorly differentiated histologies and unfavorable prognoses without medication. Pleomorphic carcinoma, a lung cancer that includes a mixed conventional histology and sarcomatoid components, is an extremely aggressive tumor and rarely responds well to anticancer treatments. However, it has recently been reported that lung cancer with a sarcomatoid component contains the ALK gene rearrangement. Therefore, we used a next-generation sequencing (NGS) analysis of the driver gene mutations in pleomorphic carcinoma (PC) of the lung to identify druggable target molecules.
Methods:
We selected PCs from primary lung carcinomas by reviewing the records of 944 patients who had undergone surgical resection between 2007 and 2014. The Ion PGM™ NGS sequencer (Life Technology Inc., US) was used to identify known gene rearrangements in lung cancers by analyzing RNA with IonAmpliSeq™ RNA Lung FusionPanel® (Life Technology). With our original panel for targeted gene amplifications, the Ion PGM was also used to analyze nucleotide sequence of whole exons of 41 driver genes reported to be involved in lung cancers. The cases examined were also analyzed with ALK immunohistochemistry (ALK-IHC) using the N-Histofine® ALK Detection Kit (Nichirei Bioscience Inc., Tokyo, Japan) on sliced paraffin-embedded tumor specimens.
Results:
Twenty-one lung cancer specimens diagnosed as PC and frozen material from nine patients were available for NGS. The EML4ex6/ALKex20 fusion gene was detected in one case, which was also positive on ALK–IHC. No other fusion genes were detected. Another case, which was negative for the fusion gene, was weakly positivity on ALK–IHC, so an unbalanced 5¢/3¢-end ALK expression test is planned. Six of nine cases but not the ALK-fusion-positive cases showed driver gene mutations in TP53. We also found several somatic mutations in druggable genes in this study, which should be considered carefully to determine whether they are driver or passenger genes.
Conclusion:
Although a small number of PCs were examined in this study, the ALK fusion gene was detected, which indicates the frequency of ALK fusion might be high in PC. Other possible druggable gene mutations were also identified in PCs. Further cases must be investigated to understand the mutation status of driver genes in PC.
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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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P3.04-048 - Rare Gene Mutations in Japanese Surgically Resected Non-Small-Cell Lung Cancer Patients (ID 2715)
09:30 - 09:30 | Author(s): T. Nishii
- Abstract
Background:
Driver gene mutations except for EGFR are rare in Japanese population. In this study, we investigated EGFR, KRAS, BRAF and PIK-3 mutations in surgically resected non-small-cell lung cancer (NSCLC).
Methods:
A total of 388 consecutive patients with NSCLC who underwent complete tumor resection in our hospital from 2006 through 2008 were studied retrospectively. Formalin-fixed, paraffin-embedded tissue sections were used to isolate DNA from carcinoma lesions. Mutational analyses of EGFR, KRAS, BRAF and PIK-3 were performed by loop-hybrid mobility shift assay, a highly sensitive polymerase chain reaction-based method.
Results:
We identified 185 EGFR mutations (47.7%), 33 KRAS mutations (8.5%), 3 BRAF mutations (0.77%), and 4 PIK-3 mutations (1.03%). In patients with BRAF mutation, all three patients were adenocarcinomas and smokers. There was no mutual mutation with EGFR and KRAS. PIK-3 mutations include 2 adenocarcinomas and 2 squamous cell carcinomas. Three of 4 patients were smoker. We found one PIK-3 and EGFR double mutation case.
Conclusion:
In Japanese surgically resected NSCLC, there are a lot of EGFR mutations, but there was little KRAS mutation. Although new molecular targeted therapy is expected, BRAF and PIK-3 mutations were very rare. Highly smoking rate in patients with KRAS and BRAF mutations was not different from past reports, but we could not find other clinical characteristics. Histopathologically, correlation between PIK-3 mutation and small cell carcinoma is attracting attention recently. In this study, histological types of cases with PIK-3 mutation were various.
