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L. Mas
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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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P2.04-030 - Activating and Resistance Mutations of EGFR in Peruvian Patients with Metastatic NSCLC (ID 380)
09:30 - 09:30 | Author(s): L. Mas
- Abstract
Background:
The evaluation of EGFR mutational status of the EGFR in non-small cell lung cancer (NSCLC) is crucial to select the adequate targeted therapy and to know the prognostic of patients. Our aim was describe to determine the frequency of activating and resistance mutations of EGFR in a large cohort of Peruvian patients.
Methods:
We tested metastatic tumor samples from 436 NSCLC patients for known EGFR mutations involving exon 18 (G719X), exon 19 (deletions), exon 20 (T790M, S768I and insertions) and exon 21 (L858R). Samples were from a mutational testing program sponsored by a pharmaceutical company. All samples were processed at a central reference laboratory (Roe laboratory, Lima-Peru) under protocolized laboratory procedures.
Results:
A total of 398 out of 436 samples were evaluable for determination of EGFR mutational status. Fifty five percent of patients were male. EGFR mutations was present in 36.7% of cases (n = 146). In regard to specific mutations, G719X (in exon 18) was present in 1% (n = 4); deletions in exon 19 had a frequency of 19.6% (n = 78). Mutations in exon 20 were present in 3.5% (n = 14). In patients with exon 20 mutated, 8 cases had insertions, 5 cases had the mutation T790M and 1 case had the mutation S768I. Mutation L858R (exon 21) in 14.1% (n = 56) of cases. Coexistence of two mutations were present in exon 19/exon 20 (n = 3) and exon 20/ exon 21 (n = 3). Female patients were more likely to have any EGFR mutation with a Relative Risk = 1.92 and a P < 0.001, in the Chi-square test. In tumors with EGFR mutated. The sensible profile for EGFR tyrosine kinase inhibitors (TKI´s) was present in 94.5% of cases (n=138) while 8 cases (5.5%) had mutations associated with resistance to TKI´s.
Conclusion:
Most patients with metastatic NSCLC and EGFR mutations will benefit from anti-EGFR targeted therapy. Our frequency of EGFR activating or resistance mutation was similar to other Latin American countries where mutations in exon 19 are the most frequent.
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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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P3.04-112 - Repeated Observation of Immune Gene Sets Enrichment in Women with Non-Small Cell Lung Cancer (ID 768)
09:30 - 09:30 | Author(s): L. Mas
- Abstract
Background:
There are different patterns of lung cancer (LC) characteristics between men and women. Females tend to present LC at a younger age and with more advanced stages than males; however, the prognostic is better in women. In despite of the great advances in the knowledge of the genomic landscape of lung cancer, it is not explored the molecular differences regarding to gender. Our aim was to evaluate differentially enriched gene sets between women and men.
Methods:
We evaluated 05 public databases containing gene expression values from NSCLC patients: GSE50081 (HG-U133_Plus_2; n=81 samples), GSE47115 (Illumina HumanHT-12 WG-DASL V4.0 R2; 16 samples), GSE10072 (HG-U133A; n=71 samples), GSE32863 (Illumina HumanWG-6 v3.0; 116 samples), GSE7670 (HG-U133A; n=52 samples). In each dataset, expression levels were log2 transformed and median centered. We performed the Gene Set Enrichment Analysis (GSEA) to find differences between the two genders. Each dataset was analyzed individually. Since the smoking status is the main confounding factor, datasets were divided in cohorts of smokers and non-smokers (and healthy tissues by smoking status when it was included in the dataset). Cases with unknown smoking status and former smokers were excluded from the analysis. We use the Gene ontology biological process terms to find similar enriched pathways between cohorts, 1454 gene sets named by gene ontology terms were examined. We consider a gene set enriched when at least a cohort had a p-value<0.05 and also the observation was repeated in other datasets with a p-values <0.08 (statistical trends).
Results:
The analysis showed repeated observation of immune genes enrichment in women; defense response to virus was enriched in four data sets; cytokine biosynthetic process, innate immune response, positive regulation of cytokine biosynthetic process, regulation of cytokine biosynthetic process and response to other organism were enriched in three dataset; adaptive immune response, B cell activation, cellular defense response, chemokine activity, innate immune response, interferon gamma biosynthetic process, interleukin 8 production and others were enriched in at least two data sets. On the other hand, aminoacid transport, cellular protein catabolic process, maintenance of protein localization, regulation of GTPase activity, regulation of protein polymerization, regulation of Rho GTPase cctivity and others were enriched in three datasets in men.
Conclusion:
The analysis of global gene expression showed that Immune genes sets are frequently enriched in women compared to men. Differences on enrichment pathways between men and women should be deeply explored.
