At least 17 genomic regions are established as harboring melanoma susceptibility variants, in most instances with genome-wide levels of significance and replication in independent samples. Based on genome-wide single nucleotide polymorphism (SNP) data augmented by imputation to the 1,000 Genomes reference panel, we have fine mapped these regions in over 5,000 individuals with melanoma (mainly from the GenoMEL consortium) and over 7,000 ethnically matched controls. A penalized regression approach was used to discover those SNP markers that most parsimoniously explain the observed association in each genomic region. For the majority of the regions, the signal is best explained by a single SNP, which sometimes, as in the tyrosinase region, is a known functional variant. However in five regions the explanation is more complex. At the CDKN2A locus, for example, there is strong evidence that not only multiple SNPs but also multiple genes are involved. Our results illustrate the variability in the biology underlying genome-wide susceptibility loci and make steps toward accounting for some of the "missing heritability."
COBISS.SI-ID: 1846907
We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanoma-susceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
COBISS.SI-ID: 1472635
Avtorji v izvirnem članku opišejo pomen adjuvantnega obsevanja pri bolnikih po ingvinalni limfadenktomiji.
COBISS.SI-ID: 1162107
Background. The purpose of the study was to evaluate the ability of ultrasound(US) and fine needle aspiration biopsy (FNAB) in reducing the numberof melanoma patients requiring a sentinel node biopsy (SNB); to compare the amount of metastatic disease in regional lymph nodes in SNB candidates with clinically uninvolved lymph nodes and of those with US uninvolved lymph nodes; and to compare the overall survival (OS) of both groups. Methods. Between 2000 and 2007, a SNB was successfully performed in 707 patients with melanoma. The preoperative US of the regional lymph node basins was performed in 405 SNB candidates. In 14 of these patients, the US-guided FNAB was positive and they proceeded directly to lymph node dissection. In 391 patients, the preoperative US was either negative (343 patients) or suspicious(48 patients) (US group). In the remaining 316 patients the preoperative US was not performed (non-US group). Results. The proportion of macrometastatic sentinel lymph nodes (SN), number of metastatic lymph nodes per patient and proportion of nonsentinel lymph node metastases were found to be lower in the US group compared to the non-US group. The smaller tumour burden of the US group was reflected in a significantly better OS of patients with SN metastases. Conclusions. The preoperative US of regional lymph nodes spares some patients with melanoma from undergoing a SNB. Patients with regional metastases and a negative preoperative US have a significantly lower tumour burden in comparison to those with clinically negative lymph nodes, which is also reflected in a better OS.
COBISS.SI-ID: 29627609
The aim of this study was to evaluate the effect of a residual melanoma after an excisional biopsy on prognosis of patients with cutaneous melanoma. PATIENTS AND METHODS: Between 2000 and 2007 sentinel lymph node biopsy with wide reexcision of a primary melanoma site was successfully performed in 692 patients (315 male and 377 female; mean age 55.7 years) at the Institute of Oncology Ljubljana, Slovenia. Clinicopathological data of all patients were extracted from a prospective institutional melanoma database and the frequency of local recurrences and survival were compared between patients with residual melanoma and those without it. For a statistical analysis univariate and multivariate analyses were used. RESULTS: Only 25 (3.6%) patients had a residual melanoma. There was no difference in mean tumor thickness (3.9 and 2.8 mm) and ulceration (40% and 34%) of the primary melanoma between patients with and without residual melanoma. However, a number of local recurrences (16% versus 2.7%) and a number of metastases in sentinel lymph nodes (44% versus 22%) were significantly higher and a 5-year survival was significantly lower (64% versus 87.5%) in patients with residual melanoma. Breslow thickness, ulceration, positive SLNB and residual melanoma were independent prognostic factors for overall survival. CONCLUSIONS: Residual melanoma is very rare after an excisional biopsy of the primary melanoma. However, when present it indicates a higher probability of local recurrence and a worse overall survival.
COBISS.SI-ID: 1937787