This work provides a comprehensive CpG methylation landscape of the different layers of the human eye that unveils the gene networks associated with their biological functions and how these are disrupted in common visual disorders. Herein, we firstly determined the role of CpG methylation in the regulation of ocular tissue-specification and described hypermethylation of retinal transcription factors (i.e., PAX6, RAX, SIX6) in a tissue-dependent manner. Second, we have characterized the DNA methylome of visual disorders linked to internal and external environmental factors. Main conclusions allow certifying that crucial pathways related to Wnt-MAPK signaling pathways or neuroinflammation are epigenetically controlled in the fibrotic disorders involved in retinal detachment, but results also reinforced the contribution of neurovascularization (ETS1, HES5, PRDM16) in diabetic retinopathy. Finally, we had studied the methylome in the most frequent intraocular tumors in adults and children (uveal melanoma and retinoblastoma, respectively). We observed that hypermethylation of tumor suppressor genes is a frequent event in ocular tumors, but also unmethylation is associated with tumorogenesis. Interestingly, unmethylation of the proto-oncogen RAB31 was a predictor of metastasis risk in uveal melanoma. Loss of methylation of the oncogenic mir-17-92 cluster was detected in primary tissues but also in blood from patients.

The tumor suppressor gene TP53 and its regulator MDM2 are both key players involved in multiple pathways including apoptosis, cellular transcriptional control and cell cycle regulation. Common germline polymorphisms in these genes may affect colorectal cancer (CRC) susceptibility. An arginine-to-proline substitution at codon 72 in the TP53 gene is reported to decrease apoptotic potential, while a thymine-to-guanine polymorphism at nucleotide 309 (named SNP309) of murine double minute 2 MDM2 gene increases its transcription. These two polymorphisms therefore may be of importance in colorectal carcinogenesis. The relation of these polymorphisms to colorectal cancer in the Algerian population was addressed in this study. DNA samples from 121 controls and 116 cases were genotyped for these two polymorphisms by PCR/RFLP then confirmed by sequencing. Unexpectedly no significant association was found between this potential marker TP53 Arg72Pro and CRC (p > 0.05). However, our findings reveal that individuals with the MDM2 SNP309 GG genotype have a low risk of CRC as compared to the TT genotype (OR = 0.49; 95 % CI: 0.24-0.98, p = 0.04), with more significance for females (OR = 0.16; 95 % CI: 0.06-0.41, p < 0.05). Moreover, no significant association was observed between the combined TP53 and MDM2 genotypes and CRC. Contrary to initial expectations that the GG genotype with high MDM2 levels would increase cancer risk, our results demonstrate that the MDM2 SNP309 GG genotype is associated with decreased risk of colorectal cancer. This is suggesting that other mechanisms independent of increased MDM2 levels can influence cancer susceptibility.

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Une mutation des deux allèles du gène Rb durant le développement rétinien norma est responsable de l’apparition du rétinoblastome. La recherche de mutations au niveau du gène Rb reste difficile, car la majorité des altérations sont uniques et dispersées tout au long du gène. Nous rapportons dans notre étude le résultat de l’analyse du gène Rb au niveau constitutionnel et tumoral dans la population algérienne.Notre étude a porté sur un échantillon de 21 patients atteints de rétinoblastome. Le promoteur et les 27 exons avec leurs séquences introniques flanquantes composant le gène Rb ont été amplifiés et analysés par HPLC (chromatographie liquide à haute performance) suivie d’un séquençage. Les variations de bases identifiées au niveau constitutionnel et tumoral sont au nombre de 7 dont 3 mutations non sens, une mutation affectant le site d’épissage, une délétion et 2 polymorphismes. L’analyse du gène Rb a été réalisée chez des enfants atteints de rétinoblastome ne présentant aucun antécédent familial de la maladie. Par cette étude, nous avons pu identifier deux cas sur les 21 étudiés ayant un rétinoblastome pouvant être transmissible.Deux mutations rapportées n’ont jamais été décrites dans la littérature.