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| Author(s): |
Wanessa Cardoso da Silva
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2017-05-17 |
| Examining board members: |
Telma Miyuki Oshiro Sumida;
Maria Notomi Sato
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| Advisor: | Telma Miyuki Oshiro Sumida; Alessandra Pontillo |
| Abstract | |
Melanoma, the most aggressive form of skin cancer, is a malignant melanocyte tumor. In addition to environmental risks such as UV radiations, individual\'s skin phenotype and genetics has also been described as potential risk factors for the development of melanoma. It has recently been reported that malignant melanoma is directly related to the constitutive secretion of the inflammatory cytokine, IL-1?, in transformed melanocytes suggesting the involvement of the inflammasome in tumor progression. In order to evaluate if the genetics of the inflammasome could contribute to the susceptibility to the development of malignant melanoma, we analyzed 10 single nucleotide polymorphisms (SNPs) in five inflammation related genes (NLRP1, NLRP3, CARD8, IL1B, IL18) in a case/control Brazilian cohort of melanoma. In addition, the expression of inflammatory genes was evaluated in biopsies of melanoma and nevus tumors. We recruited 198 melanoma patients and 142 healthy donors. Tumor/nevus biopsies were obtained from 15 of 198 melanoma patients and five of 142 healthy controls, respectively. We used the real-time PCR technique for specific allele with specific probes using TaqMan ® assays for genotyping of DNA samples from melanoma cases/controls and for studies of expression of specific genes of inflammasome from RNA samples of tumor biopsy and nevus, respectively. We have found that SNP rs6509365 in CARD8 was significantly more common in healthy controls than in melanoma patients, suggesting a protective effect of this variant for the development of melanoma. Corroborating this finding, CARD8 expression was found to be increased in melanoma biopsies compared to nevus expression. In addition, stratification of the data showed that variant rs11651270 in NLRP1 was associated with nodular melanoma; rs1143643 in IL1B at low levels was associated with invasiveness (Breslow score) and rs5744256 in IL18 was associated with melanoma development in sun sensitive individuals. Biopsy analysis of tumors further showed that IL-1? expression was up-regulated, especially in samples from individuals who had metastases, whereas IL-18 was down-regulated compared to expression in nevus. Together our results demonstrated for the first time the contribution of the inflammation related genes CARD8, IL1B and IL18 to melanoma (AU) | |
| FAPESP's process: | 12/18448-5 - Analysis of inflammasome in melanoma: correlation between tumoral cells and immune response mediated by dendritic cells |
| Grantee: | Wanessa Cardoso da Silva |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |