Distribution of KRAS, DDR2, and TP53 gene mutations in lung cancer: An analysis of Iranian patients

Abstract

PurposeLung cancer is the deadliest known cancer in the world, with the highest number of mutations in proto-oncogenes and tumor suppressor genes. Therefore, this study was conducted to determine the status of hotspot regions in DDR2 and KRAS genes for the first time, as well as in TP53 gene, in lung cancer patients within the Iranian population.Experimental designThe mutations in exon 2 of KRAS, exon 18 of DDR2, and exons 5–6 of TP53 genes were screened in lung cancer samples, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) using PCR and sequencing techniques.ResultsAnalysis of the KRAS gene showed only a G12C variation in one large cell carcinoma (LCC) patient, whereas variants were not found in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) cases. The Q808H variation in the DDR2 gene was detected in one SCC sample, while no variant was seen in the ADC and LCC subtypes. Variations in the TP53 gene were seen in all NSCLC subtypes, including six ADC (13.63%), seven SCC (15.9%) and two LCC (4.54%). Forty-eight variants were found in the TP53 gene. Of these, 15 variants were found in coding regions V147A, V157F, Q167Q, D186G, H193R, T211T, F212L and P222P, 33 variants in intronic regions rs1625895 (HGVS: c.672+62A>G), rs766856111 (HGVS: c.672+6G>A) and two new variants (c.560-12A>G and c.672+86T>C).ConclusionsIn conclusion, KRAS, DDR2, and TP53 variants were detected in 2%, 2.17% and 79.54% of all cases, respectively. The frequency of DDR2 mutation is nearly close to other studies, while KRAS and TP53 mutation frequencies are lower and higher than other populations, respectively. Three new putative pathogenic variants, for the first time, have been detected in Iranian patients with lung cancer, including Q808H in DDR2, F212L, and D186G in coding regions of TP53. In addition, we observed five novel benign variants, including Q167Q, P222P and T211T in coding sequence, and c.560-12A>G and c.672+86T>C, in intronic region of TP53. Mutations of KRAS and DDR2 were found in LCC and SCC subtypes, respectively, whereas mutations of TP53 were seen in SCC and ADC subtypes with higher frequencies and LCC subtype with lower frequency. Therefore, Iranian lung cancer patients can benefit from mutational analysis before starting the conventional treatment. A better understanding of the biology of these genes and their mutations will be critical for developing future targeted therapies.

A Preliminary Study of the Complement Component 1q Levels in Predicting the Efficacy of Combined Immunotherapy in Patients with Lung Cancer

“…Exploring the genetic background of different populations is of great significance to predict lung cancer patients’ response to immunotherapies. 11 In the application of ICIs, immune-related adverse events (irAEs) are the key monitoring items in clinical practice. The incidence of all grade irAEs is 22%, and that of high-grade irAEs is 4%.…”

Overall survival in patients with lung adenocarcinoma harboring “niche” mutations: an observational study

“…The main feature that characterizes these "niche" mutations is their low prevalence in the population of patients with lung cancer when compared with KRAS and EGFR. In the present study, we identified these "niche mutations" on the basis of a population prevalence that was equal to or less than 10% based on literature data [8][9][10]. In particular, according to recently published data concerning 14 healthcare institutions in the US, the prevalence for these mutations was as follows: KRAS 25%, EGFR 23%, HER2 2.7%, BRAF 2.6%, PIK3CA 0.8%, NRAS 0.7%, c-MET 0.7%, and MAP2K1 0.3% [8].…”

“…In particular, according to recently published data concerning 14 healthcare institutions in the US, the prevalence for these mutations was as follows: KRAS 25%, EGFR 23%, HER2 2.7%, BRAF 2.6%, PIK3CA 0.8%, NRAS 0.7%, c-MET 0.7%, and MAP2K1 0.3% [8]. Moreover, the prevalence of the RET mutation in adenocarcinoma was estimated to be 1.7% [9], and the prevalence of DDR2 mutation in lung cancer was 2.2% [3,10]. Overall, the KRAS mutation was considered to be the most lethal mutation, exhibiting the worst prognosis [3][4][5].…”

Methylation of TGM-3 Promoter and Its Association with Oral Squamous Cell Carcinoma (OSCC)

“…DNA extraction was performed based on the classic phenol-chloroform extraction method with some modifications 26 , 27 . Briefly, 20 mg of the tissue sample was homogenized in 400 μl of lysis buffer (10 mM NaCl, 20 mM Tris-HCl, 1 mM EDTA, pH=8), 50 μl of 10% SDS, and 25 μl of proteinase k (10 mg/ml ).…”