P-116 Characteristics of P53 gene mutations in Polish non small cell lung cancer (NSCLC) patients

e21014 Background: In targeted therapy for patients with advanced non-small cell lung cancer (NSCLC), approximately 30% of NSCLC patients with EGFR mutations develop primary resistance at the beginning of treatment with TKIs. However, the knowledge of primary resistance in early-stage NSCLC patients with EGFR positve remains poorly understood. Methods: Mutations of nine genes that may be related to primary resistance EGFR TKIs in advanced non-small cell lung cancer were chosen through pubmed and other databases including EGFR T790M, EGFR 20ins, PIK3CA, KRAS, BRAF, ERBB2 amplification, MET amplification, PTEN deletion and BCL2L11 deletion. Gene mutations related to primary resistance in patients with early-stage lung cancer (I-IIIA) from the TCGA database were analyzed. Results: According to TCGA database, there were 1089 patients with NSCLC of which 585 were lung adenocarcinoma and 504 lung were squamous cell carcinoma. A number of 46 EGFR-sensitive (19del / L858R) mutations were observed in adenocarcinoma, of which the clinical information of which 44 cases harbored competed clinical information including 39 patients with early stage could be identified as follows,1 patient in stage I, 11 patients in stage IA, 8 patients in stage IB, 7 patients in stage IIA, 4 patients in stage IIB, 8 patients in stage IIIA, 1 patient in stage IIIB and 4 patients in stage IV, respectively. Among the 39 cases of early non-small cell lung cancer with EGFR-sensitive mutations, 2 case of EGFR T790M mutations (5.12%), 2 case of PIK3CA (5.12%), 2 case of BRAF (5.12%), 11 case of MET (DUP) (28.2 %), 8 case of ERBB2 (DUP) (20.5%) and 5 case of PTEN (Del) (12.8%) mutations were observed respectively. Meanwhile, none of primary resistance gene mutations could be found in non-small cell lung squamous cell cancer(0/1). Conclusions: The presence of different mutation frequency in the primary resistance genes associated with EGFR TKIs in patients with early NSCLC was proved. Our study suggested it was necessary for patients to test mutations in primary resistance genes before accepted the adjuvant and neoadjuvant therapy using TKIs. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.

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REV3L Gene Variants rs1002481, rs462779, and rs465646 Lead to Increased Susceptibility Towards Non-Small Cell Lung Cancer in the Population of Jammu and Kashmir.

10.21203/rs.3.rs-42137/v1 ◽

2020 ◽

Author(s):

Rajeshwar Singh Jamwal ◽

Nikita Mahajan ◽

Gh. Rasool Bhat ◽

Amrita Bhat ◽

Bhanu Sharma ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Strong Association ◽

Gene Mutations ◽

Small Cell ◽

Small Cell Lung ◽

Jammu And Kashmir ◽

Nsclc Patients

Abstract Background: Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer accounting for 80–85% of all lung cancer cases. Various genetic studies have tried to reveal the association of REV3L (Protein reversion less 3-like) gene mutations with cancer, including lung cancer but no such study has been carried out in the population of Jammu and Kashmir (J&K).Methods: The selected REV3L variants were genotyped using the TaqMan allele discrimination assay in 550 subjects (203 NSCLC patients and 347 healthy controls). The association of variants was evaluated by logistic regression.Results: Out of the four REV3L variants genotyped, we found rs1002481, rs462779, and rs465646 significantly associated with NSCLC risk with an Odds Ratio (OR) of 3.5 (1.98–6.3 at 95% CI ), p value = 0.00002; OR = 4.4 (1.8–10.4 at 95% CI ), p value = 0.00075; and OR = 2.4 (1.47–4.008 at 95% CI ), p value = 0.00053, respectively.Conclusion: Our data suggest a strong association of variants rs1002481, rs462779, rs465646 with NSCLC. This association is indicative of a potential role of mutations in the REV3L gene as risk factor for the development of NSCLC in the studied population. Although a first report from any Indian population, these variants have been previously reported to be associated with lung and colorectal cancers in different world populations. These data along with our data supports the notation that these variants can be used as potential prognostic biomarker.

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