Distinct pattern of oxidative DNA damage and DNA repair in follicular thyroid tumours

Karger, S.; Krause, Kerstin; Engelhardt, C.; Weidinger, Carl; Gimm, Oliver; Dralle, Henning; Sheu-Grabellus, Sien-Yi; Schmid, Kurt Werner; Führer, Dagmar

doi:10.1530/jme-11-0119

Cited by 24 publications

(21 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A recent study demonstrated that multinodular thyroid was the most frequent kind of internal tumor in XP-C patients [16], while adenocarcinoma of the thyroid was reported in only one 18-year-old XP-C patient [20]. This might be due to the accumulation of oxidative damage in the thyroid [21]. …”

Section: Discussionmentioning

confidence: 99%

Further Evidence of Mutational Heterogeneity of theXPCGene in Tunisian Families: A Spectrum of Private and Ethnic Specific Mutations

Rekaya

Jerbi

Messaoud

et al. 2013

BioMed Research International

View full text Add to dashboard Cite

Xeroderma Pigmentosum (XP) is a rare recessive autosomal cancer prone disease, characterized by UV hypersensitivity and early appearance of cutaneous and ocular malignancies. We investigated four unrelated patients suspected to be XP-C. To confirm linkage to XPC gene, genotyping and direct sequencing of XPC gene were performed. Pathogenic effect of novel mutations was confirmed by reverse Transciptase PCR. Mutation screening revealed the presence of two novel mutations g.18246G>A and g.18810G>T in the XPC gene (NG_011763.1). The first is present in one patient XP50NEF, but the second is present in three unrelated patients (XP16KEB, XP28SFA, and XP45GB). These 3 patients are from three different cities of Southern Tunisia and bear the same haplotype, suggesting a founder effect. Reverse Transciptase PCR revealed the absence of the XPC mRNA. In Tunisia, as observed in an other severe genodermatosis, the mutational spectrum of XP-C group seems to be homogeneous with some clusters of heterogeneity that should be taken into account to improve molecular diagnosis of this disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Further Evidence of Mutational Heterogeneity of theXPCGene in Tunisian Families: A Spectrum of Private and Ethnic Specific Mutations

Rekaya

Jerbi

Messaoud

et al. 2013

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Increased nuclear levels of 8-oxo-dG were found in both benign (human follicular adenomas or FTAs) and malignant (follicular (FTC) and PTC) lesions in comparison with matched normal tissue (Young et al 2010, Karger et al 2012; this most likely reflects the deleterious impact of a long-term exposure to chronic oxidative stress that is observed during thyroid malignancy. Interestingly, an investigation of the link between BER gene expression and human thyroid malignancy showed a reduction in OGG1 expression in FTC compared to FTA (Karger et al 2012). TCGA data analysis highlights a downregulation of the expression level of OGG1 in papillary thyroid tumours with a high level of MAPK1 expression, which reflects the activation of the MAPK signalling pathway ( Fig.…”

Section: Oxidative Dna Damage In Thyroid Carcinomasmentioning

confidence: 93%

“…In mouse models, the levels of oxidative DNA damage in the thyroid gland were higher than those in any other organ, with high levels of thyroid OGG1 mRNA expression (Maier et al 2006). Increased nuclear levels of 8-oxo-dG were found in both benign (human follicular adenomas or FTAs) and malignant (follicular (FTC) and PTC) lesions in comparison with matched normal tissue (Young et al 2010, Karger et al 2012; this most likely reflects the deleterious impact of a long-term exposure to chronic oxidative stress that is observed during thyroid malignancy. Interestingly, an investigation of the link between BER gene expression and human thyroid malignancy showed a reduction in OGG1 expression in FTC compared to FTA (Karger et al 2012).…”

Section: Oxidative Dna Damage In Thyroid Carcinomasmentioning

confidence: 99%

Oxidative stress in thyroid carcinomas: biological and clinical significance

Hassani

Buffet

Leboulleux

et al. 2019

Endocrine-Related Cancer

View full text Add to dashboard Cite

At physiological concentrations, reactive oxygen species (ROS), including superoxide anions and H2O2, are considered as second messengers that play key roles in cellular functions, such as proliferation, gene expression, host defence and hormone synthesis. However, when they are at supraphysiological levels, ROS are considered potent DNA-damaging agents. Their increase induces oxidative stress, which can initiate and maintain genomic instability. The thyroid gland represents a good model for studying the impact of oxidative stress on genomic instability. Indeed, one particularity of this organ is that follicular thyroid cells synthesise thyroid hormones through a complex mechanism that requires H2O2. Because of their detection in thyroid adenomas and in early cell transformation, both oxidative stress and DNA damage are believed to be neoplasia-preceding events in thyroid cells. Oxidative DNA damage is, in addition, detected in the advanced stages of thyroid cancer, suggesting that oxidative lesions of DNA also contribute to the maintenance of genomic instability during the subsequent phases of tumourigenesis. Finally, ionizing radiation and the mutation of oncogenes, such as RAS and BRAF, play a key role in thyroid carcinogenesis through separate and unique mechanisms: they upregulate the expression of two distinct ‘professional’ ROS-generating systems, the NADPH oxidases DUOX1 and NOX4, which cause DNA damage that may promote chromosomal instability, tumourigenesis and dedifferentiation.

show abstract

“…Neben der ähnlichen Morphologie ist das Vorliegen identischer Genmutationen ein Argument für die Existenz einer Adenom-Karzinom-Sequenz in der follikulären Karzinogenese. Hingegen unterscheiden sich beide Entitäten in anderen molekulargenetischen Merkmalen, u. a. der antioxidativen Antwort, dem Muster der oxidativen Schädigung und der Aktivierung von Zellzyklus-Checkpoints [15,16,22,33]. 11,19,34,39].…”

Section: Follikuläres Adenomunclassified

Molekulare Pathogenese von Schilddrüsenknoten – Bedeutung für die klinische Versorgung

2016

View full text Add to dashboard Cite

Zusammenfassung Schilddr?senknoten stellen heterogene Tumore dar, mit unterschiedlichen molekularen Signaturen. W?hrend benigne Schilddr?senknoten poly- oder monoklonalen Tumoren entsprechen, sind Schilddr?senkarzinome monoklonale und damit ?echte? Neoplasien. Urs?chlich f?r die Neoplasien sind somatische Mutationen, welche zur konstitutiven Aktivierung spezifischer Signalkaskaden f?hren und den jeweiligen histologischen, teilweise auch den funktionellen Ph?notyp des Schilddr?sentumors bestimmen. Eine Dedifferenzierung von Schilddr?senkarzinomen geht mit dem Auftreten weiterer Mutationen in den Tumoren einher. Die Mutationslast der Schilddr?senkarzinome korreliert mit deren biologischem Verhalten. Im klinischen Alltag kann die Kenntnis der urs?chlichen somatischen Mutation in der zytologischen Differenzialdiagnose helfen. In der prognostischen Einsch?tzung von Schilddr?sentumoren hat der Nachweis von klassischen Onkogenmutationen (BRAF, RAS) wenig Relevanz. Andere genetische Ver?nderungen, insbesondere TERT Promoter Mutationen, die mit zunehmender H?ufigkeit in fortgeschrittenen SD-Karzinomen auftreten, haben wahrscheinlich eine prognostische Bedeutung. Von gro?er Relevanz ist die molekulare Signatur jedoch f?r die Entwicklung und Anwendung passgenauer ?zielgerichteter? Therapien bei fortgeschrittenen Karzinomen (radioiodrefrakt?res DTC, PDTC und ATC, metastasiertes medull?res Karzinom). Hierf?r gibt es aus klinischen Studien sowie Einzelfallberichten zunehmend Hinweise, die das Konzept der ?Oncogen-Addiction? als pathogenetisch relevanten Mechanismus der SD-Tumorigenese und Karzinogenese unterstreichen.

show abstract

Distinct pattern of oxidative DNA damage and DNA repair in follicular thyroid tumours

Cited by 24 publications

References 37 publications

Further Evidence of Mutational Heterogeneity of theXPCGene in Tunisian Families: A Spectrum of Private and Ethnic Specific Mutations

Further Evidence of Mutational Heterogeneity of theXPCGene in Tunisian Families: A Spectrum of Private and Ethnic Specific Mutations

Oxidative stress in thyroid carcinomas: biological and clinical significance

Molekulare Pathogenese von Schilddrüsenknoten – Bedeutung für die klinische Versorgung

Contact Info

Product

Resources

About