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. 2018 Aug;26(8):1188-1193.
doi: 10.1038/s41431-018-0149-8. Epub 2018 Apr 30.

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

Miriam Potrony  1   2 , Joan Anton Puig-Butille  2   3 , James M Farnham  4 , Pol Giménez-Xavier  1   2 , Celia Badenas  2   3 , Gemma Tell-Martí  1   2 , Paula Aguilera  1   2 , Cristina Carrera  1   2 , Josep Malvehy  1   2 , Craig C Teerlink  4 , Susana Puig  5   6
Affiliations

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

Miriam Potrony et al. Eur J Hum Genet. 2018 Aug.

Abstract

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.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Genome-wide het-TLOD scores. Genome-wide het-TLOD scores in dominant (continuous line) and recessive (dashed line) models are plotted. Significant linkage evidence threshold (het-TLOD >3.3) is denoted by the horizontal dashed line
Fig. 2
Fig. 2
Genome-wide TLOD scores for family #1. Genome-wide TLOD scores for dominant (continuous plot line) and recessive (dashed plot line) models are plotted. The suggestive linkage evidence threshold (TLOD >1.9) is denoted by the horizontal dashed line
See this image and copyright information in PMC

References

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