Evaluation of loss of heterozygosity and microsatellite instability in human pterygium: clinical correlations

Detorakis, Εfstathios T.; Sourvinos, George; Tsamparlakis, J; Spandidos, Demetrios Α.

doi:10.1136/bjo.82.11.1324

Cited by 53 publications

(52 citation statements)

References 20 publications

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“…Genetic lesions previously detected in pterygia, such as LOH and mutations to P53 4 were, in some cases, directly correlated to the level of exposure to UVR or were located in regions with known susceptibility to UVR, such as 9q or 17p. 5 In the present study, Ki-ras mutations were not detected in conjunctival specimens excised from areas located under the upper eyelid and thus protected from the solar light. However, mutations to N-ras, which have been reported to be highly susceptible to UVR, 10,11 were not detected in any case.…”

Section: Discussioncontrasting

confidence: 43%

“…However, mutations to N-ras, which have been reported to be highly susceptible to UVR, 10,11 were not detected in any case. Furthermore, the altitude of residence, which is correlated with the exposure to UVR, 5 was not significantly higher in patients displaying Ki-ras mutations. Therefore, although absent in areas with less exposure to solar light, mutations detected could be independent of the action of UVR.…”

Section: Discussionmentioning

confidence: 83%

“…3 There is growing evidence that pterygium is a proliferative, rather than degenerative, condition. 4 Experimental findings, such as detection of loss of heterozygosity (LOH), 4,5 association with oncogenic viruses, 6 and mutations in p53, 7 as well as clinical evidence, such as progressive growth and frequent postoperative recurrences, 1,5 support the concept that pterygium may be considered a benign neoplastic condition. Based on immunohistochemistry with monoclonal antibodies against p53 and vimentin, it has been proposed that pterygia may arise from a vimentin-expressing, altered limbal epithelial basal cell, the so-called 'pterygium cell' 8 However, the exact molecular events leading to pterygium development are not clear.…”

Section: Introductionmentioning

confidence: 94%

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Detection of point mutations at codon 12 of KI-ras in ophthalmic pterygia

Detorakis

Zafiropoulos

Arvanitis

et al. 2004

Eye

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Aims Ophthalmic pterygium is a potentially vision-threatening lesion of unknown etiology, related to an exposure to solar light. Mutations to the ras genes are frequently observed in lesions related to an exposure to solar light. The present study aims at screening pterygia for mutations at codons 12 and 13 of the ras genes. Methods In all, 50 pterygia were examined, together with respective blood samples and specimens of normal conjunctiva. A PCR reaction was performed to amplify sequences containing codons 12 and 13 of Ki-ras, H-ras, and N-ras. An RFLP analysis was then performed to detect point mutations at codon 12. The mutational status at codons 12 and 13 was further explored with sequencing of PCR products.Results RFLP analysis revealed Ki-ras mutations at codon 12 in five (10%) of pterygia, whereas H-ras or N-ras mutations were not observed. Sequencing confirmed Ki-ras mutations at codon 12 and revealed absence of mutations at codon 13. The presence of Ki-ras mutations was significantly correlated with postoperative recurrence (P ¼ 0.02) and young age (P ¼ 0.04). Mutations were not observed in specimens of blood or normal conjunctiva for any of the genes examined. Conclusions The absence of N-ras mutations is in agreement with previous reports concerning mucosal lesions. The detection of Ki-ras mutations and the association with postoperative recurrence implies a possible role of Ki-ras in the clinical profile of pterygium. The mechanism of Ki-ras mutations is unclear and could be independent of the action of UV light.

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Section: Discussioncontrasting

confidence: 43%

Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 94%

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Detection of point mutations at codon 12 of KI-ras in ophthalmic pterygia

Detorakis

Zafiropoulos

Arvanitis

et al. 2004

Eye

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“…FGF2 expression was significantly higher in larger pterygia of >3 mm on the corneal surface, compared with pterygia of smaller size, implying that FGF2 may be involved in the clinical behavior of some pterygia and in particular with the tendency of some pterygia to display progressive growth. Altitude of residence (which is in turn associated with the levels of exposure to UV radiation) (7) did not correlate with FGF2, which may be attributed to either the relatively small number of patients studied or to the fact that these patients (irrespective of their specific location of residence) were exposed to environmental factors such as high levels of sunshine.…”

Section: Discussionmentioning

confidence: 91%

Growth factor expression in ophthalmic pterygia and normal conjunctiva

Detorakis

Zaravinos²,

Spandidos³

2010

Int J Mol Med

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Abstract. The expression of growth factors in ophthalmic pterygium and phenotypically normal conjunctiva was examined and correlated with the clinical findings. Fifteen specimens of ophthalmic pterygia and 8 specimens of phenotypically normal conjunctiva were examined. Total RNA was extracted from all specimens and mRNA levels for transforming growth factor (TGFB1), vascular endothelial growth factor (VEGFA), basic fibroblast growth factor (FGF2), epidermal growth factor (EGF) and insulin-like growth factor (IGF1) were measured using real-time reversetranscription PCR (qRT-PCR). Differences in the expression of these factors between pterygium and conjunctival specimens were examined, as well as correlations between RNA levels and clinical parameters. mRNA levels for VEGFA and FGF2 were significantly higher in pterygium, compared with conjunctival specimens, whereas the respective differences for other factors examined were statistically not significant. The mRNA levels for VEGFA and FGF2 were also significantly higher in recurrent compared with primary pterygium. Correlations between the mRNA levels and other clinical parameters were statistically not significant for the growth factors examined. The higher levels of FGF2 or VEGFA mRNA in pterygium imply that these factors may be involved in the pathogenesis or clinical behavior of the pterygium, including postoperative recurrence. VEGFA expression may have potential for use in the selective treatment of pterygium with anti-VEGFA agents.

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“…However, pterygia display some tumourlike properties in their clinical appearance of local invasion and epithelial cell metaplasia. 2 Furthermore, the presence of oncogenic viruses, such as the human papilloma virus and herpes simplex virus, 3,4 loss of heterozygosity, 5 and abnormal p53 expression in pterygium lesions, 6,7 all suggest the possible neoplastic nature of pterygium. A model of pterygium formation is then proposed, in which genetic predisposition, environmental factors, and viral infections may participate in the multistep process.…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphism of hOGG1 and risk of pterygium in Chinese

Hc¹,

Cc²,

Wm³

et al. 2004

Eye

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Purpose Ultraviolet irradiation is known to cause oxidative DNA damage and is thought to be a major factor implicated in the pathogenesis of pterygium. The highly mutagenic 8-hydroxy-2 0 -deoxyguanosine, a marker for the evaluation of photo-oxidative DNA damage, can be repaired by human 8-oxoguanine glycosylase I (hOGG1). A transition of C to G at nucleotide position 1245 in exon 7 of the hOGG1 gene is associated with the substitution of cysteine for serine at codon 326. In this study, we investigated the association of the hOGG1 Ser326Cys polymorphism with pterygium in a Chinese population. Methods In all, 70 patients and 86 controls were enrolled in this study. The Ser326Cys polymorphism was determined by the polymerase chain reaction-restriction fragment-length polymorphism analysis. The association between this genetic polymorphism and risk of pterygium was examined by w 2 -test and logistic regression. Results The allelic frequencies for the Ser and Cys variants of hOGG1 gene were not significantly different between the two groups. However, when compared with Ser/ Ser and Ser/Cys genotypes combined, we found that the homozygous Cys/Cys genotype was more prevalent in pterygium patients than controls (P ¼ 0.024) with the odds ratio being 2.2 (95% CI: 1.1-4.5). In the pterygium group, the mean age of patients with the Cys/Cys genotype was younger than those with the other two genotypes (P ¼ 0.025). Conclusions Our findings suggest that the 1245C-G transition in exon 7 of the hOGG1 gene, which results in Ser326Cys substitution of the enzyme, might play a role in the susceptibility of humans to pterygium.

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Evaluation of loss of heterozygosity and microsatellite instability in human pterygium: clinical correlations

Cited by 53 publications

References 20 publications

Detection of point mutations at codon 12 of KI-ras in ophthalmic pterygia

Detection of point mutations at codon 12 of KI-ras in ophthalmic pterygia

Growth factor expression in ophthalmic pterygia and normal conjunctiva

Genetic polymorphism of hOGG1 and risk of pterygium in Chinese

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