Micronucleus analysis in patients with colorectal adenocarcinoma and colorectal polyps

Karaman, Ali̇; Binici, Doğan Nasır; Kabalar, Mehmet Eşref; Çalıkuşu, Züleyha

doi:10.3748/wjg.14.6835

Cited by 29 publications

(13 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, healthy women with BRCA1 and BRCA2 mutations showed a higher increase in MN frequency and a higher radiation sensitivity than women without family history of breast cancer (Rothfuss et al, 2000; Trenz et al, 2003). Similar outcomes were shown in lung cancer patients with a high frequency of spontaneous MN (Guler et al, 2005), as well as in patients with pleural malignant mesothelioma (Bolognesi et al, 2002), and adenocarcinoma patients (Karaman et al, 2008). Cancer-prone patients with Bloom syndrome and ataxia telangiectasia also possess a high frequency of MN in lymphocytes (Rosin and German, 1985).…”

Section: The Fate Of Micronuclei In Cellssupporting

confidence: 65%

Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond

Luzhna¹,

Kathiria²,

Kovalchuk³

2013

Front. Genet.

347

203

View full text Add to dashboard Cite

Micronuclei (MN) are extra-nuclear bodies that contain damaged chromosome fragments and/or whole chromosomes that were not incorporated into the nucleus after cell division. MN can be induced by defects in the cell repair machinery and accumulation of DNA damages and chromosomal aberrations. A variety of genotoxic agents may induce MN formation leading to cell death, genomic instability, or cancer development. In this review, the genetic and epigenetic mechanisms of MN formation after various clastogenic and aneugenic effects on cell division and cell cycle are described. The knowledge accumulated in literature on cytotoxicity of various genotoxins is precisely reflected and individual sensitivity to MN formation due to single gene polymorphisms is discussed. The importance of rapid MN scoring with respect to the cytokinesis-block micronucleus assay is also evaluated.

show abstract

Section: The Fate Of Micronuclei In Cellssupporting

confidence: 65%

Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond

Luzhna¹,

Kathiria²,

Kovalchuk³

2013

Front. Genet.

347

203

View full text Add to dashboard Cite

show abstract

“…Our findings suggest that this phenotype might represent the largest molecular class of hereditary CRC defined to date. Classic cytogenetic studies in PBLs from patients with colon and other cancers have noted increased micronuclei, a marker of genomic instability 32–34 . Moreover, while our manuscript was under review, it was reported that lymphocytes from colon cancer patients exhibit on average greater comet sizes 35 .…”

Section: Discussionmentioning

confidence: 99%

Genetic Variants That Predispose to DNA Double-Strand Breaks in Lymphocytes From a Subset of Patients With Familial Colorectal Carcinomas

et al. 2015

View full text Add to dashboard Cite

BACKROUND & AIMS DNA structural lesions are prevalent in sporadic colorectal cancer, so we proposed that gene variants that predispose to DNA double-strand breaks (DSBs) would be found in patients with familial colorectal carcinomas of an undefined genetic basis (UFCRC). METHODS We collected primary T cells from 25 patients with UFCRC and matched patients without colorectal cancer (controls) and assayed for DSBs. We performed exome sequence analyses of germline DNA from 20 patients with UFCRC and 5 undiagnosed patients with polyposis. The prevalence of identified variants in genes linked to DNA integrity was compared to that of individuals without a family history of cancer. The effects of representative variants found to be associated with UFCRC was confirmed in functional assays with HCT116 cells. RESULTS Primary T cells from most patients with UFCRC had increased levels of the DSB marker γH2AX following treatment with DNA damaging agents, compared to T cells from controls (P<.001). Exome sequence analysis identified a mean 1.4 rare variants/patient that were predicted to disrupt functions of genes relevant to DSBs. Controls (from public databases) had a much lower frequency of variants in the same genes (P<.001). Knockdown of representative variant genes in HCT116 CRC cells increased γH2AX. Detailed analysis of immortalized patient-derived B cells, which contained variants in the Werner syndrome, RecQ helicase-like gene (WRN, encoding T705I), and excision repair cross-complementation group 6 (ERCC6, encoding N180Y), revealed reduced levels of these proteins and increased DSBs, compared to B cells from controls. This phenotype was rescued by exogenous expression of WRN or ERCC6. Direct analysis of the recombinant variant proteins confirmed defective enzymatic activities. CONCLUSIONS These results provide evidence that defects in suppression of DSBs underlie some cases of UFCRC; these can be identified by assays of circulating lymphocytes. We specifically associated UFCRC with variants in WRN and ERCC6 that reduce capacity for repair of DNA DSBs. These observations could lead to a simple screening strategy for UFCRC, and provide insight into the pathogenic mechanisms of colorectal carcinogenesis.

show abstract

“…Bloom syndrome or ataxia telangiectasia, have abnormally high MN frequencies [45]. Moreover, Karaman et al [30] observed a significant increase in MN level in the lymphocytes of patients with colorectal adenocarcinoma and with neoplastic polyps. Hamurcu et al [22] showed a clear increase in the frequency of MN in peripheral lymphocytes in untreated cancer patients.…”

Section: Discussionmentioning

confidence: 99%

“…UC-associated colorectal cancer occurs as a result of genetic and molecular abnormalities, such as alterations in tumor suppressor genes, oncogenes and genes encoding DNA repair proteins, as well as by an overall loss of genomic stability, similar to that seen in sporadic colorectal cancer [14,15,29,30]. Chromosomal instability is the most frequently occurring form of genomic instability in UC-associated cancers [29].…”

Section: Discussionmentioning

confidence: 99%

Investigation of Genome Instability in Exfoliated Colonic Epithelial Cells and in Mitogen-Stimulated Lymphocytes of Patients with Ulcerative Colitis

Karaman

Hamurcu²,

Dönmez³

et al. 2012

Digestion

View full text Add to dashboard Cite

Objective: The present study aimed to evaluate the micronucleus (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in the mitogen-stimulated lymphocytes of patients with ulcerative colitis (UC). In addition, we assessed MN frequency in exfoliated colonic epithelial cells obtained from both the diseased and healthy colonic mucosa of patients. Design: The study was conducted in 22 newly diagnosed patients with UC and in 22 healthy controls. MN, NPB and NBUD values scored in binucleated (BN) cells were obtained from the mitogen-stimulated lymphocytes of patients and control subjects. In addition, the MN values in exfoliated epithelial cells obtained from the diseased and healthy colonic mucosa of patients were evaluated. Results: We found significantly higher MN, NPB and NBUD frequencies in the BN cells of patients with UC than in those of the control subjects (1.61 ± 0.75 vs. 0.89 ± 0.29, 3.93 ± 1.91 vs. 1.39 ± 1.10, and 1.55 ± 0.89 vs. 0.64 ± 0.48, p = 0.001). Also, a statistically significant difference was found between MN frequencies obtained from the diseased and healthy colonic mucosa of patients (1.07 ± 0.46 vs. 0.59 ± 0.21, p = 0.001). No significant relationship was found between age and MN frequency in patients with UC (r = 0.076, p = 0.735). Conclusion: Increased MN, NPB and NBUD frequencies observed in both the lymphocytes and exfoliated colonic epithelial cells obtained from patients with UC may reflect genomic instability.

show abstract

Micronucleus analysis in patients with colorectal adenocarcinoma and colorectal polyps

Cited by 29 publications

References 47 publications

Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond

Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond

Genetic Variants That Predispose to DNA Double-Strand Breaks in Lymphocytes From a Subset of Patients With Familial Colorectal Carcinomas

Investigation of Genome Instability in Exfoliated Colonic Epithelial Cells and in Mitogen-Stimulated Lymphocytes of Patients with Ulcerative Colitis

Contact Info

Product

Resources

About