EGFR exon 19‐deletion aberrantly regulate ERCC1 expression that may partly impaired DNA damage repair ability in non‐small cell lung cancer

Zhang, Linlin; Pradhan, Barun; Guo, Lili; Fang, Meng; Zhong, Diansheng

doi:10.1111/1759-7714.13253

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…Our previous report indicated that the association between the increase in 8‐OH‐dG levels due to human papillomavirus (HPV) 16/18 infection and the occurrence of EGFR mutations in patients with NSCLC might be due to a reduction in DNA repair capabilities 19 . Other groups have reported an association between lower ERCC1 expression, the SNP rs744154c in ERCC4 , and EGFR exon 19 deletion mutations, thereby revealing the possibility that EGFR exon 19 deletion mutations could be associated with decreasing DNA repair capabilities 20,21 . In the present study, we observed that EGFR deletion mutations in exon 19 were more common in patients with hOGG1 ‐Cys variants with less ability to remove 8‐OH‐dG than with hOGG1 Ser/Ser genotype.…”

Section: Discussionsupporting

confidence: 58%

Association of hOGG1‐Cys variants with occurrence of p53 and EGFR deletion mutations in non‐small cell lung cancer

et al. 2020

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Background The human 8‐oxoguanine DNA glycosylase 1 (hOGG1) gene encodes a DNA glycosylase that removes 8‐hydroxy‐2‐deoxyguanine (8‐OH‐dG) DNA damage to protect against gene mutations. The association of hOGG1 Ser326Cys polymorphism with lung cancer risk has predicted that hOGG1‐Cys variants are less effective at removing 8‐OH‐dG damage from DNA; therefore, these variants might show an increased occurrence of tumor suppressor gene and oncogene mutations. However, no evidence has yet supported this hypothesis. Methods Direct sequencing was performed to examine the mutations of p53 and EGFR genes in lung tumors from patients with non‐small cell lung cancer (NSCLC). Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) was used to examine hOGG1 Ser326Cys polymorphism in this study population. Results A total of 99 p53‐mutated and 99 EGFR‐mutated patients with NSCLC were selected to explore the possible associations of these mutations with hOGG1 Ser326Cys polymorphism. The p53‐mutated and EGFR‐mutated patients were divided into nondeletion and deletion subgroups. P53 deletion mutations were more commonly observed in male than in female patients (P = 0.030). However, EGFR exon 19 deletion mutations were more prevalent in female and adenocarcinoma patients than in male and squamous cell carcinoma patients (P = 0.028 for genders, P = 0.017 for tumor histology). Interestingly, p53 and EGFR exon 19 deletion mutations were more frequent in patients with hOGG1 Ser/Cys + Cys/Cys hOGG1‐Cys variants than with the hOGG1 Ser/Ser genotype (P = 0.010 for p53, P = 0.032 for EGFR). Conclusions We suggest that the association of hOGG1 Ser326Cys polymorphism with lung cancer risk could be partially explained by increases in p53 and EGFR deletion mutations. Key points Significant findings of the study NSCLC patients with hOGG1‐Cys variants may have a higher risk of p53 and EGFR deletion mutations than with hOGG1 Ser/Ser genotype. What this study adds NSCLC patients with hOGG1‐Cys variants might be helpful to predict patients having higher risk of EGFR exon 19 deletion mutations and these patients who were treated with gefitinib or erlotinib could be a higher risk to occur EGFR T790M mutation.

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Section: Discussionsupporting

confidence: 58%

Association of hOGG1‐Cys variants with occurrence of p53 and EGFR deletion mutations in non‐small cell lung cancer

et al. 2020

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“…This can be explained by different effects of EGFR and KRAS driver mutations on DNA repair. Driver www.nature.com/scientificreports/ mutations in EGFR are associated with decreased DNA repair capacity in non-small cell lung cancer 72 . KRAS driver mutations, on the other hand, are associated with more efficient DNA repair in lung tumors 73 which may contribute to poor response of KRAS driver mutation-positive tumors to radiotherapy 74 .…”

Section: Discussionmentioning

confidence: 99%

Strength of selection in lung tumors correlates with clinical features better than tumor mutation burden

Gorlov,

Gorlova,

Tsavachidis

et al. 2024

Sci Rep

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Single nucleotide substitutions are the most common type of somatic mutations in cancer genome. The goal of this study was to use publicly available somatic mutation data to quantify negative and positive selection in individual lung tumors and test how strength of directional and absolute selection is associated with clinical features. The analysis found a significant variation in strength of selection (both negative and positive) among tumors, with median selection tending to be negative even though tumors with strong positive selection also exist. Strength of selection estimated as the density of missense mutations relative to the density of silent mutations showed only a weak correlation with tumor mutation burden. In the “all histology together” analysis we found that absolute strength of selection was strongly correlated with all clinically relevant features analyzed. In histology-stratified analysis selection was strongest in small cell lung cancer. Selection in adenocarcinoma was somewhat higher compared to squamous cell carcinoma. The study suggests that somatic mutation- based quantifying of directional and absolute selection in individual tumors can be a useful biomarker of tumor aggressiveness.

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“…When DNA damage fails to be repaired or excised, the mutations will eventually trigger carcinogenesis. For instance, epidermal growth factor receptor (EGFR) exon 19 deletion corrected with decreased expression of ERCC1 impacts ERCC1 foci formation in response to DNA cross-link damage, contributing to DNA damage repair (DDR) deficiency ( 14 ). Germline variants of ataxia-telangiectasia mutated (ATM), tumor suppressor 53 protein (TP53), breast cancer 2 (BRCA2), EGFR, and Parkinson’s Disease-Associated protein 2 (PARK2) had been linked to cancer risk in Mendelian disorders ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review

Mao,

Lee,

Saad

et al. 2024

Transl Lung Cancer Res

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Despite significant advancements in screening, diagnosis, and treatment of non-small cell lung cancer (NSCLC), it remains the primary cause of cancer-related deaths globally. DNA damage is caused by the exposure to exogenous and endogenous factors and the correct functioning of DNA damage repair (DDR) is essential to maintain of normal cell circulation. The presence of genomic instability, which results from defective DDR, is a critical characteristic of cancer. The changes promote the accumulation of mutations, which are implicated in cancer cells, but these may be exploited for anti-cancer therapies. NSCLC has a distinct genomic profile compared to other tumors, making precision medicine essential for targeting actionable gene mutations. Although various treatment options for NSCLC exist including chemotherapy, targeted therapy, and immunotherapy, drug resistance inevitably arises. The identification of deleterious DDR mutations in 49.6% of NSCLC patients has led to the development of novel target therapies that have the potential to improve patient outcomes. Synthetic lethal treatment using poly (ADP-ribose) polymerase (PARP) inhibitors is a breakthrough in biomarker-driven therapy. Additionally, promising new compounds targeting DDR, such as ATR, CHK1, CHK2, DNA-PK, and WEE1, had demonstrated great potential for tumor selectivity. In this review, we provide an overview of DDR pathways and discuss the clinical translation of DDR inhibitors in NSCLC, including their application as single agents or in combination with chemotherapy, radiotherapy, and immunotherapy.

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EGFR exon 19‐deletion aberrantly regulate ERCC1 expression that may partly impaired DNA damage repair ability in non‐small cell lung cancer

Cited by 7 publications

References 27 publications

Association of hOGG1‐Cys variants with occurrence of p53 and EGFR deletion mutations in non‐small cell lung cancer

Association of hOGG1‐Cys variants with occurrence of p53 and EGFR deletion mutations in non‐small cell lung cancer

Strength of selection in lung tumors correlates with clinical features better than tumor mutation burden

Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review

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