Dataset Information

Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with lentigo maligna melanoma in a Mediterranean population.

ABSTRACT: Cutaneous melanoma tumour is classified into clinicohistopathological subtypes that may be associated with different genetic and host factors. Variation in the MC1R gene is one of the main factors of risk variation in sporadic melanoma. The relationship between MC1R variants and the risk of developing a specific subtype of melanoma has not been previously explored.To analyse whether certain MC1R variants are associated with particular melanoma subtypes with specific clinicohistopathological features.An association study was performed between MC1R gene variants and clinicopathological subtypes of primary melanoma derived from 1679 patients.We detected 53 MC1R variants (11 synonymous and 42 nonsynonymous). Recurrent nonsynonymous variants were p.V60L (30·0%), p.V92M (11·7%), p.D294H (9·4%), p.R151C (8·8%), p.R160W (6·2%), p.R163Q (4·2%) p.R142H (3·3%), p.I155T (3·8%), p.V122M (1·5%) and p.D84E (1·0%). Melanoma subtypes showed differences in the total number of MC1R variants (P = 0·028) and the number of red hair colour variants (P = 0·035). Furthermore, an association between p.R163Q and lentigo maligna melanoma was detected under a dominant model of heritance (odds ratio 2·16, 95% confidence interval 1·07-4·37; P = 0·044). No association was found between p.R163Q and Fitzpatrick skin phototype, eye colour or skin colour, indicating that the association was independent of the role of MC1R in pigmentation. No association was observed between MC1R polymorphisms and other melanoma subtypes.Our findings suggest that certain MC1R variants could increase melanoma risk due to their impact on pathways other than pigmentation, and may therefore be linked to specific melanoma subtypes.

SUBMITTER: Puig-Butille JA

PROVIDER: S-EPMC3863403 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with lentigo maligna melanoma in a Mediterranean population.

Puig-Butillé J A JA Carrera C C Kumar R R Garcia-Casado Z Z Badenas C C Aguilera P P Malvehy J J Nagore E E Puig S S

The British journal of dermatology 20131001 4

<h4>Background</h4>Cutaneous melanoma tumour is classified into clinicohistopathological subtypes that may be associated with different genetic and host factors. Variation in the MC1R gene is one of the main factors of risk variation in sporadic melanoma. The relationship between MC1R variants and the risk of developing a specific subtype of melanoma has not been previously explored.<h4>Objectives</h4>To analyse whether certain MC1R variants are associated with particular melanoma subtypes with ...[more]

PMID: 23647022

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Project description:Importance:The management of lentigo maligna (LM) and LM melanoma (LMM) is challenging because of extensive subclinical spread and its occurrence on cosmetically sensitive areas. Reflectance confocal microscopy (RCM) improves diagnostic accuracy for LM and LMM and can be used to delineate their margins. Objectives:To evaluate whether handheld RCM with radial video mosaicing (HRCM-RV) offers accurate presurgical assessment of LM and LMM margins. Design, Setting, and Participants:This prospective study included consecutive patients with biopsy-proven LM and LMM located on the head and neck area who sought consultation for surgical management from March 1, 2016, through March 31, 2017, at the Dermatology Service of the Memorial Sloan Kettering Cancer Center. Thirty-two patients underwent imaging using HRCM-RV, and 22 patients with 23 LM or LMM lesions underwent staged surgery and contributed to the analysis. Main Outcomes and Measures:Clinical lesion size and area, LM and LMM area based on HRCM-RV findings, surgical defect area estimated by HRCM-RV, and observed surgical defect area. In addition, the margins measured in millimeters estimated for tumor clearance in each quadrant based on HRCM-RV findings were calculated and compared with the surgical margins. Results:Among the 22 patients (12 men and 10 women; mean [SD] age, 69.0 [8.6] years [range, 46-83 years]) with 23 lesions included in the final analysis, the mean (SD) surgical defect area estimated with HRCM-RV was 6.34 (4.02) cm2 and the mean (SD) area of surgical excision with clear margins was 7.74 (5.28) cm2. Overall, controlling for patient age and previous surgery, surgical margins were a mean of 0.76 mm (95% CI, 0.67-0.84 mm; P?<?.001) larger than the HRCM-RV estimate. Conclusions and Relevance:Mapping of LM and LMM with HRCM-RV estimated defects that were similar to but slightly smaller than those found in staged excision. Thus, mapping of LM using HRCM-RV can help spare healthy tissue by reducing the number of biopsies needed in clinically uncertain areas and may be used to plan treatment of LM and LMM and counsel patients appropriately.

Project description:ImportanceLentigo maligna (LM) presents an invasive component in up to 20% of biopsied cases, but to date the histologic features useful in detecting this invasive component have not been described. Some histologic characteristics are hypothesized to contribute to the progression of LM invasion.ObjectiveTo identify the histologic characteristics associated with lentigo maligna melanoma (LMM) in patients with LM diagnosed by a partial diagnostic biopsy.Design, setting, and participantsA retrospective cross-sectional study of patients treated between January 1, 2000, and December 31, 2017, was conducted in a referral oncology center in València, Spain. Data and specimens of patients (n = 96) with a diagnosis of primary cutaneous melanoma in the form of either LM or LMM who had undergone surgical treatment, a complete histologic examination of the whole tumor, and an initial diagnostic partial biopsy of LM were included in the study. Histologic assessment was blinded to the presence of an invasive component.InterventionsAll biopsy specimens were evaluated for the presence of certain histologic characteristics.Main outcomes and measuresComparisons between invasive samples and samples without an invasive component were performed. The differences in the distribution of variables between the groups were assessed using the χ2 and Fisher exact tests, and the degree of association of the relevant variables was quantified by logistic regression models. A classification and regression tree analysis was performed to rank the variables by importance.ResultsIn total, 96 patients had sufficient histologic material that could be evaluated. The patients were predominantly male (56 [58.3%]) and had a mean (SD) age at diagnosis of 72 (12) years. Of these patients, 63 (65.6%) had an LM diagnosis and 33 (34.4%) had an LMM diagnosis (an invasive component). The histologic variables associated with the presence of an invasive component were melanocytes forming rows (odds ratio [OR], 11.5; 95% CI, 1.4-94.1; P = .02), subepidermal clefts (OR, 2.8; 95% CI, 1.0-7.9; P = .049), nests (OR, 3.0; 95% CI, 1.1-8.6; P = .04), and a lesser degree of solar elastosis (OR, 0.4; 95% CI, 0.1-1.1; P = .07). A classification and regression tree analysis of the relevant histologic features was able to accurately identify lentigo maligna with an invasive component (LMM) in more than 60% of patients.Conclusions and relevanceThese findings may be useful in classifying early LM specimens at higher risk of invasion, which may eventually be relevant in identifying the most appropriate management for LM.

Dataset Information

Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with lentigo maligna melanoma in a Mediterranean population.

Publications

Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with lentigo maligna melanoma in a Mediterranean population.

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