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T. Kohno
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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: 2
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-037 - Prevalence of NRG1 Fusions in Caucasian NSCLC Patients Determined by Fluorescence in Situ Hybridisation (ID 1553)
09:30 - 09:30 | Author(s): T. Kohno
- Abstract
Background:
Fusions of the gene Neuregulin1 (NRG1) have been described to activate PI3K-AKT signaling in NSCLC via NRG1 overexpression and binding to Her2/Neu-Her3. NRG1 fusions were detected in pulmonary mucinous adenocarcinoma of Asian non-smokers lacking other known oncogenic driver mutations. The incidence in such patients has been described to be between 17.6% (6/34) and 44.4% (4/9). NRG1 fusions might be targeted by Her2/Her3-inhibitors and clinical trials are planned. Here we describe for the first time the systematic analysis of NRG1 in Caucasian patients by Fluorescence in situ hybridization (FISH).
Methods:
A ZytoLight®-based FISH assay (ZytoVision, Bremerhaven, Germany) was developed and verified on nine published clinical cases with known NRG1 fusions. A total of 160 Caucasian NSCLC patients were screened. 25 of the cases were mucinous adenocarcinoma lacking a known oncogenic driver mutation as determined by deep-sequencing and FISH tests. 135 cases were pulmonary adenocarcinoma of various subtypes including 35 cases that lacked a driver mutation and 100 cases that were EGFR, ALK and ROS1 wildtype. The smoking-status was not evaluated. Statistics were calculated using R 3.1.0 .
Results:
The NRG1 fusions in the published cases were easily detected by the FISH assay. However, none of the screened cases harbored a NRG1 fusion. The result is significant compared to published reference values of 17.6% (p=0.041) and 44.4% (p<0.001). The theoretical maximum incidence of NRG1 fusions among Caucasian NSCLC patients not stratified by smoking-status was calculated to be <16.6% for mucinous adenocarcinomas lacking driver mutations, <7.5% for adenocarcinoma of all morphological subtypes lacking driver mutations and <3% for EGFR, ALK, ROS1 negative pulmonary adenocarcinoma (95% confidence intervals).
Conclusion:
FISH is a suitable technique to screen for NRG1 fusions in pulmonary adenocarcinoma. Among 160 Caucasian patients including 25 mucinous carcinomas lacking a driver mutation none were NRG1 positive. Thus, the incidence among Caucasian patients appears to be low and should be evaluated in studies of large NSCLC cohorts.
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P3.04-110 - PTPRH Hypomethylation as a Prognostic Factor in Non-Small Cell Lung Cancer (ID 759)
09:30 - 09:30 | Author(s): T. Kohno
- Abstract
Background:
Tyrosine phosphorylation is an important signaling mechanism in cancer. PTPRH is a receptor-type protein tyrosine phosphatase thought to be a potential regulator of tumorigenesis. The aim of this study is to clarify the significance of PTPRH expression and its regulation by DNA methylation in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma.
Methods:
PTPRH mRNA expression was examined in 89 NSCLC and corresponding non-cancerous tissues. The correlation between DNA methylation and PTPRH gene expression was investigated in another cohort that consisted of 145 patients with lung adnocarcinoma. Gene regulation by DNA methylation was assessed using a DNA methylation inhibitor. Statistic analysis was performed to clarify whether the DNA methylation status of PTPRH is a prognostic factor for patients with lung adenocarcinoma.
Results:
PTPRH mRNA expression was significantly up-regulated in NSCLC. PTPRH DNA methylation was reduced in lung ademocarcinomas and inversely correlated with mRNA expression. 5-aza-2'-deoxycytidine treatment of lung cancer cell lines with low PTPRH expression, restored mRNA PTPRH expression levels. Furthermore, low PTPRH methylation was associated with shorter recurrence-free survival (P < 0.0002) and overall survival (P < 0.0001). Multivariate analysis revealed that PTPRH DNA methylation was an independent prognostic factor (P < 0.01).
Conclusion:
We confirmed that PTPRH is overexpressed in NSCLC. In addition, we determined that hypomethylation of PTPRH is a poor prognostic factor in lung adenocarcinoma.
