Genome-wide linkage analysis in Spanish melanoma-prone families identifies a new familial melanoma susceptibility locus at 11q

 

The main genetic factors for familial melanoma remain unknown in >75% of families. CDKN2A is mutated in around 20% of melanoma-prone families. Other high-risk melanoma susceptibility genes explain <3% of families studied to date. We performed the first genome-wide linkage analysis in CDKN2A-negative Spanish melanoma-prone families to identify novel melanoma susceptibility loci. We included 68 individuals from 2, 3, and 6 families with 2, 3, and at least 4 melanoma cases. We detected a locus with significant linkage evidence at 11q14.1-q14.3, with a maximum het-TLOD of 3.449 (rs12285365:A>G), using evidence from multiple pedigrees. The genes contained by the subregion with the strongest linkage evidence were: DLG2, PRSS23, FZD4, and TMEM135. We also detected several regions with suggestive linkage evidence (TLOD >1.9) (1q, 6p, 7p, 11q, 12p, 13q) including the region previously detected in melanoma-prone families from Sweden at 3q29. The family-specific analysis revealed three loci with suggestive linkage evidence for family #1: 1q31.1-q32.1 (max. TLOD 2.447), 6p24.3-p22.3 (max. TLOD 2.409), and 11q13.3-q21 (max. TLOD 2.654). Future next-generation sequencing studies of these regions may allow the identification of new melanoma susceptibility genetic factors.

https://www.ncbi.nlm.nih.gov/pubmed/29706638

#acralmelanoma  #melanoma  #susanapuig #josepmalvehy #cristinacarrera #skincancer #paulaaguilera  #thegooddoctor #topdoctors #familialmelanoma #cdkn2a #skincancer #skinmelanoma  

Ugly Duckling Sign as a Major Factor of Efficiency in Melanoma Detection

Importance:

Understanding the contribution of the ugly duckling sign (a nevus that is obviously different from the others in a given individual) in intrapatient comparative analysis (IPCA) of nevi may help improve the detection of melanoma.

Objectives:

To assess the agreement of dermatologists on identification of the ugly duckling sign and estimate the contribution of IPCA to the diagnosis of melanoma.

Design, Setting, and Participants:

The same 2089 digital images of the nevi of a sample of 80 patients (mean age, 42 years [range, 19-80 years]; 33 men and 47 women), as well as 766 dermoscopic images from a subset of 30 patients (mean age, 40 years [range, 21-75 years]; 12 men and 18 women), were randomly presented to the same 9 dermatologists for blinded assessment from September 22, 2011, to April 1, 2013. The first experiment was designed to mimic an IPCA situation, with images of all nevi of each patient shown to the dermatologists, who were asked to identify ugly duckling nevi (UDN). The second experiment was designed to mimic a lesion-focused analysis to identify morphologically suspicious nevi. Data analysis was conducted from November 1, 2012, to June 1, 2013.

Main Outcomes and Measures:

Number of nevi labeled UDN and morphologically suspicious nevi, specificity of lesion-focused analysis and IPCA, and number of nevi identified for biopsy.

Results:

Of the 2089 clinical images of nevi from 80 patients (median number of nevi per patient, 26 [range, 8-81]) and 766 dermoscopic images (median number of nevi per patient, 19 [range, 8-81]), all melanomas were labeled UDN and as morphologically suspicious nevi by the 9 dermatologists. The median number of UDN detected per patient was 0.8 among the clinical images of nevi (mean, 1.0; range, 0.48-2.03) and 1.26 among the dermoscopic images (mean, 1.4; range, 1.00-2.06). The propensity to consider more or fewer nevi as having ugly duckling signs was independent of the presentation (clinical or dermoscopic). The agreement among the dermatologists regarding UDN was lower with dermoscopic images (mean pairwise agreement, 0.53 for clinical images and 0.50 for dermoscopic images). The specificity of IPCA was 0.96 for clinical images and 0.95 for dermoscopic images vs 0.88 and 0.85, respectively, for lesion-focused analysis. When both IPCA and lesion-focused analyses were used, the number of nevi considered for biopsy was reduced by a factor of 6.9 compared with lesion-focused analysis alone.

Conclusions and Relevance:

Intrapatient comparative analysis is of major importance to the effectiveness of the diagnosis of melanoma. Introducing IPCA using the ugly duckling sign in computer-assisted diagnosis systems would be expected to improve performance.

#josepmalvehy #clinicadermatologica #dermatologobarcelona #melanoma #cancerdepiel #diagnosismelanoma #canceruña #skincancer #dermatologabarcelona #bestdoctor #topdoctors #nevus #confocal #susanapuig

Prognostic role of the histological subtype of melanoma on the hands and feet in Caucasians.

PubMed

Prognostic role of the histological subtype of melanoma on the hands and feet in Caucasians.

Acral melanoma (AM) is associated with a poor prognosis in part because of delayed diagnosis, but probably also because of other intrinsic characteristics of location. The aim of this study was to review the specific characteristics and outcome of AM in Caucasians.

This was a cross-sectional retrospective clinical-pathological study of 274 patients identified with AM in the database of a referral unit in Europe from 1986 to 2010. The mean age of the patients was 56.6 (SD 17.7) years. 269 cases could be histologically classified and included in the study. In all, 222 (82.5%) were located on feet.

According to melanoma subtype, 165 (61.3%) were acral lentiginous melanoma (ALM), 84 (31.2%) were superficial spreading melanoma (SSM), and 20 (7.5%) were nodular melanoma (NM). SSM patients were characterized by female predominance (77.4%), younger age, and classic melanoma-risk phenotype (fair skin and multiple nevi). Among the 198 invasive cases with a mean follow-up of 56.2 months, the mean (SD) Breslow's thickness was 3.1 (3.6) mm, being 1.4 (1.4) mm in SSM, 3.5 (4.1) mm in ALM and 4.9 (2.9) mm in NM (P<0.001). Ulceration was present in 33.3%, 2.9% in SSM, 38.6% in ALM, and 76.9% in NM (P<0.001). A total of 29.3% relapsed (7.3% of SSM, 35% of ALM and 55% of NM) and 24.2% died because of AM.

In multivariate analysis, age at diagnosis, Breslow, and histopathological subtype were independent prognostic factors for both disease-free and AM-specific survival. The ALM and NM subtypes presented poorer outcome after weighting Breslow and age (P=0.02). Histological subtype of AM could have an impact on biological behavior, ALM and NM subtypes presenting a poorer prognosis after adjusting for age and Breslow's thickness.

https://www.ncbi.nlm.nih.gov/pubmed/28296711

#cristinacarrera #josepmalvehy #susanapuig #breslow #melanoma #skincancer #breslowthickness #carcinoma #acrallentiginousmelanoma #alm #melanomacaucasians #acralmelanoma #melanomarisk