Author of

• 18974

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  P3.02 - Biology/Pathology (ID 620)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 24023

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    P3.02-075 - Molecular Disorders of the Genes of Intracellular Signal Pathways in Patients with Non-Small Cell Lung Cancer (ID 10070)

    09:30 - 09:30  |  Presenting Author(s): Anna Shchayuk
    • Abstract

    Background:
    Non-small cell lung cancer (NSCLC) is about 85% of all cases of lung cancer. The most common types of NSCLC are adenocarcinoma (AC) and squamous cell carcinoma (SCC). The pathogenesis of them is activated by two different tyrosine kinase cascades (RAS/RAF/MAPK and PI3K/AKT/mTOR). The genes controlling these pathways are EGFR, KRAS, PIK3CA and PTEN. Therefore, the study of disorders of these genes will help to more accurately reveal the development of a specific histological type of NSCLC. The aim of this study is to identify mutations of EGFR, KRAS, PIK3CA and PTEN genes in patients with NSCLC among the population of people living in Belarus.
    
    Method:
    The study was conducted on 106 patients (78 men, 28 women) with histologically confirmed non-small cell lung cancer (51 cases of AC, 55 cases of SCC). Analysis of mutations was performed by PCR followed by sequencing DNA, which was extracted from the tumor and non-tumor lung tissues of patients.
    
    Result:
    Analysis of associations between mutations and specific histological type of NSCLC showed that classical EGFR mutations are only in patient with AC. The frequency of them is 23.5%: deletions in exon 19 (p.E746_A750del, p.L747_P753delinsS) are 13.7%, insertions in exon 20 (p.A763_Y764insFQEA) are 7.8% and missense mutation in exon 21 (p.L858R) are 2.0%. In addition, there are detected silent mutations that have no effect on the functioning of the protein. There were mutation in intron 18 (с.2184+19G>A) and synonymous mutation in exon 21 (c.2508C>T). The frequencies of them in patients with AC are 7.8% and 3.9% respectively, in patients with SCC are 14.5% and 1.8% respectively. Analysis of mutations in exon 2 KRAS gene detected 3 types of mutations: p.G12D, p.G12C and p.G13C. The frequency of this mutations in patients with AC are 5.9%, in patients with SCC are 1.8%. No mutations of PIK3CA and PTEN genes were found. To correct the treatment of patients, it is important not only the histological type of cancer, but also the gender characteristics of the population. In the studied population, mutations of the EGFR gene were found mainly in women with AC compared to men (39.3% and 1.0%, respectively). Mutations of the KRAS gene are found only in men, and in patients with AC mutations occur 4 times more often than in patients with SCC (10.7% and 2.4%, respectively).
    
    Conclusion:
    Thus, the RAS/RAF/MAPK signal pathway plays an important role in the pathogenesis of adenocarcinoma.