Evolving insights: how DNA repair pathways impact cancer evolution

Zhou, Jiadong; Zhou, Xiao Albert; Zhang, Ning; Wang, Jiadong

doi:10.20892/j.issn.2095-3941.2020.0177

Cited by 20 publications

(13 citation statements)

References 257 publications

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“…Plasma ctDNA remains an excellent surrogate for the extracranial solid tumors in our analysis given that it shares a highly consistent GI score with the primary tumor tissue ( Figure S2 , r = 0.9, p < 0.01). As a result, the significantly higher GI scores and the higher proportion of samples with a high GI status in CSF actually reflect a difference between extracranial metastasis and MM, which could be explained by clonal evolution [ 30 ], that is, GI first occurred in the metastatic subclone of the primary tumor and then metastasized into the MM lesion to become the master clone before being detected. Another possibility is that GI occurs after MM.…”

Section: Discussionmentioning

confidence: 99%

Genomic Instability in Cerebrospinal Fluid Cell-Free DNA Predicts Poor Prognosis in Solid Tumor Patients with Meningeal Metastasis

Wang

Zhang

Han

et al. 2022

Cancers

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Genomic instability (GI), which leads to the accumulation of DNA loss, gain, and rearrangement, is a hallmark of many cancers such as lung cancer, breast cancer, and colon cancer. However, the clinical significance of GI has not been systematically studied in the meningeal metastasis (MM) of solid tumors. Here, we collected both cerebrospinal fluid (CSF) and plasma samples from 56 solid tumor MM patients and isolated cell-free ctDNA to investigate the GI status using a next-generation sequencing-based comprehensive genomic profiling of 543 cancer-related genes. According to the unfiltered heterozygous mutation data-derived GI score, we found that 37 (66.1%) cases of CSF and 3 cases (6%) of plasma had a high GI status, which was further validated by low-depth whole-genome sequencing analysis. It is demonstrated that a high GI status in CSF was associated with poor prognosis, high intracranial pressure, and low Karnofsky performance status scores. More notably, a high GI status was an independent poor prognostic factor of poor MM-free survival and overall survival in lung adenocarcinoma MM patients. Furthermore, high occurrences of the co-mutation of TP53/EGFR, TP53/RB1, TP53/ERBB2, and TP53/KMT2C were found in MM patients with a high GI status. In summary, the GI status in CSF ctDNA might be a valuable prognostic indicator in solid tumor patients with MM.

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Section: Discussionmentioning

confidence: 99%

Genomic Instability in Cerebrospinal Fluid Cell-Free DNA Predicts Poor Prognosis in Solid Tumor Patients with Meningeal Metastasis

Wang

Zhang

Han

et al. 2022

Cancers

View full text Add to dashboard Cite

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“…Genomic instability is one of the main features of tumor progression and heterogeneity ( Hanahan and Weinberg, 2011 ; Macheret and Halazonetis, 2015 ; Zhou et al, 2020 ). Research on its effect has been carried out very early during the process, and some investigators have performed preliminary experimental research.…”

Section: Discussionmentioning

confidence: 99%

Genome Instability-Associated Long Non-Coding RNAs Reveal Biomarkers for Glioma Immunotherapy and Prognosis

Wang

Zhang

et al. 2022

Front. Genet.

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Genome instability is a hallmark of tumors and is involved in proliferation, invasion, migration, and treatment resistance of many tumors. However, the relationship of genome instability with gliomas remains unclear. Here, we constructed genome instability-derived long non-coding RNA (lncRNA)-based gene signatures (GILncSig) using genome instability-related lncRNAs derived from somatic mutations. Multiple platforms were used to confirm that the GILncSig were closely related to patient prognosis and clinical characteristics. We found that GILncSig, the glioma microenvironment, and glioma cell DNA methylation-based stemness index (mDNAsi) interacted with each other to form a complex regulatory network. In summary, this study confirmed that GILncSig was an independent prognostic indicator for patients, distinguished high-risk and low-risk groups, and affected immune-cell infiltration and tumor-cell stemness indicators (mDNAsi) in the tumor microenvironment, resulting in tumor heterogeneity and immunotherapy resistance. GILncSig are expected to provide new molecular targets for the clinical treatment of patients with gliomas.

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“…Genomic instability is one of the fundamental features of cancer and contributes to the intratumoral heterogeneity. The events from genomic instability are classified into the two classes, i.e., small range aberrations such as mutation of driver genes and tumor suppressor genes, and large range aberrations due to chromosomal instability leading to the production of aneuploid cells [ 70 ]. The latter has been designated as macroevolution of cancer [ 71 ], in which various chromosomal changes result in loss of tumor suppressor genes, chimeric fusion of oncogenes, and oncogene amplifications [ 72 73 ].…”

Section: Chromosomal Instatbility and Macroevolution Of Hgscmentioning

confidence: 99%

“…ROS often causes the DNA damage with double-strand break, and dysfunction of DNA repair pathway due to HRD may accelerate the chromosomal instability ( Fig. 5 ) [ 70 ]. In addition, it has recently been hypothesized that epigenetic reprogramming precedes to various genetic or chromosomal alterations as the earliest step of carcinogenesis [ 83 84 85 ].…”

Section: Chromosomal Instatbility and Macroevolution Of Hgscmentioning

confidence: 99%

Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics

et al. 2022

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Epithelial ovarian cancer remains the lethal gynecological malignancy in women. The representative histotype is high-grade serous carcinoma (HGSC), and most patients with HGSC present at advanced stages with peritoneal dissemination. Since the peritoneal dissemination is the most important factor for poor prognosis of the patients, complete exploration for its molecular mechanisms is mandatory. In this narrative review, being based on the clinical, pathologic, and genomic findings of HGSC, chromosomal instability and epigenetic dynamics have been discussed as the potential drivers for cancer development in the fallopian tube, acquisition of cancer stem cell (CSC)-like properties, and peritoneal metastasis of HGSC. The natural history of carcinogenesis with clonal evolution, and adaptation to microenvironment of peritoneal dissemination of HGSC should be targeted in the novel development of strategies for prevention, early detection, and precision treatment for patients with HGSC.

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Evolving insights: how DNA repair pathways impact cancer evolution

Cited by 20 publications

References 257 publications

Genomic Instability in Cerebrospinal Fluid Cell-Free DNA Predicts Poor Prognosis in Solid Tumor Patients with Meningeal Metastasis

Genomic Instability in Cerebrospinal Fluid Cell-Free DNA Predicts Poor Prognosis in Solid Tumor Patients with Meningeal Metastasis

Genome Instability-Associated Long Non-Coding RNAs Reveal Biomarkers for Glioma Immunotherapy and Prognosis

Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics

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