Publications (3)11.22 Total impact
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Article: Malignant melanoma arising from a perianal fistula and harbouring a BRAF gene mutation: a case report.
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ABSTRACT: Melanoma of the anal region is a very uncommon disease, accounting for only 0.2-0.3% of all melanoma cases. Mutations of the BRAF gene are usually absent in melanomas occurring in this region as well as in other sun-protected regions. The development of a tumour in a longstanding perianal fistula is also extremely rare. More frequent is the case of a tumour presenting as a fistula, that is, the fistula being a consequence of the cancerous process, although we have found only two cases of fistula-generating melanomas reported in the literature. Here we report the case of a 38-year-old male who presented with a perianal fistula of four years of evolution. Histopathological examination of the fistulous tract confirmed the presence of malignant melanoma. Due to the small size and the central location of the melanoma inside the fistulous tract, we believe the melanoma reported here developed in the epithelium of the fistula once the latter was already formed. Resected sentinel lymph nodes were negative and the patient, after going through a wide local excision, remains disease-free nine years after diagnosis. DNA obtained from melanoma tissue was analysed by automated direct sequencing and the V600E (T1799A) mutation was detected in exon 15 of the BRAF gene. Since fistulae experience persistent inflammation, the fact that this melanoma harbours a BRAF mutation strengthens the view that oxidative stress caused by inflammatory processes plays an important role in the genesis of BRAF gene mutations.BMC Cancer 08/2011; 11:343. · 3.01 Impact Factor -
Article: Genetic polymorphisms in DNA repair and oxidative stress pathways associated with malignant melanoma susceptibility.
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ABSTRACT: Base excision repair (BER) and nucleotide excision repair (NER) pathways eliminate a wide variety of DNA damage, including UV photoproducts. The ability of each individual to repair DNA damage following different causes might explain at least in part the variability in cancer susceptibility. Moreover, inflammatory response to UV exposure may further contribute to skin carcinogenesis by oxidative stress mechanisms. Single nucleotide polymorphisms in genes encoding various DNA-repair enzymes and oxidative stress factors may be candidate low-penetrance variants with a role in susceptibility to different cancers, particularly in those with aetiologies linked to environmental exposure, such as malignant melanoma (MM). In this case-control study, 684 Spanish sporadic MM patients and 406 cancer-free control subjects were included and the role of 46 polymorphisms belonging to 16 BER and NER genes as well as 11 genes involved in oxidative stress processes were investigated. One polymorphism was identified to be individually associated with MM in the Spanish population. The variant was found in the NOS1 oxidative stress gene (rs2682826; p-value=0.01). These results suggest a putative role of oxidative stress processes in the genetic predisposition to melanoma. To the authors' knowledge, this is the largest DNA repair-related SNP study in melanoma risk conducted in the Spanish population up to now. Furthermore, it also represents a comprehensive genetic study of several oxidative stress polymorphisms tested in relation to MM susceptibility.European journal of cancer (Oxford, England: 1990) 06/2011; 47(17):2618-25. · 4.12 Impact Factor -
Article: A customized pigmentation SNP array identifies a novel SNP associated with melanoma predisposition in the SLC45A2 gene.
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ABSTRACT: As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date.PLoS ONE 01/2011; 6(4):e19271. · 4.09 Impact Factor
