CHEK2 p.Ile157Thr (c.470T>C) mutation in non-small cell lung cancer: regional experience

Purpose of the study. To determine the frequency and co-occurrence with major somatic drivers of the germline CHEK2 p.Ile157Thr mutation in patients with non-small cell lung cancer (NSCLC) in the Republic of Tatarstan.

Patients and methods. Targeted next-generation sequencing (NGS) of key oncogenes was performed on tumor tissue from 151 patients. A bibliographic search was carried out manually in Google Scholar and PubMed using the terms “CHEK2 I157T,” “p.Ile157Thr,” “c.470T>C,” “NSCLC,” “germline,” “NGS,” among others; search formulations were refined with the aid of artificial intelligence, followed by mandatory manual verification. Statistical analysis was performed in SPSS v18.0. Proportions were compared using Fisher’s exact test with a significance threshold of p < 0.05.

Results. The p.Ile157Thr variant was identified in 12 patients (7.9 %); all cases (100 %) were histologically confirmed adenocarcinomas. A positive family history of malignant tumors was recorded in 2 patients (16.7 %), and multiple primary malignancies in 2 patients (16.7 %). Concomitant driver mutations were detected in 8 patients (66.7 %): EGFR in 5 (62.5 %), while 3 patients (37.5 %) harbored mutations in KRAS (12.5 %), NRAS, and BRAF, respectively. In 4 patients (33.3 %), p.Ile157Thr was the sole molecular event. In a comparison of carriers versus non-carriers of CHEK2 p.Ile157Thr, no statistically significant differences were observed in stage distribution or in the frequency of co-occurring driver alterations (Fisher’s exact test, p > 0.05).

Conclusion. The germline CHEK2 p.Ile157Thr (c.470T>C) variant was identified in a subset of patients with lung adenocarcinoma and in several cases was accompanied by somatic driver mutations. The obtained data refine the frequency of this variant in the studied population and describe the molecular characteristics of tumors in carriers, providing a basis for further evaluation of the potential clinical relevance of CHEK2 in NSCLC.

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