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

Eur J Hum Genet 2018 08 30;26(8):1188-1193. Epub 2018 Apr 30.

Department of Dermatology, Melanoma Unit, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.

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.

Download full-text PDF

Source
http://www.nature.com/articles/s41431-018-0149-8
Publisher Site
http://dx.doi.org/10.1038/s41431-018-0149-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057984PMC
August 2018
11 Reads

Publication Analysis

Top Keywords

melanoma susceptibility
12
max tlod
12
melanoma-prone families
12
linkage evidence
12
familial melanoma
8
suggestive linkage
8
genetic factors
8
>19 11q
4
11q 12p
4
tlod >19
4
evidence tlod
4
tlod
4
12p 13q
4
13q including
4
families sweden
4
detected melanoma-prone
4
region detected
4
including region
4
identification melanoma
4
regions suggestive
4

References

(Supplied by CrossRef)

M Potrony et al.
Ann Transl Med 2015

AM Goldstein et al.
J Med Genet 2007

C Badenas et al.
Dermatol Ther 2012

SA Leachman et al.
J Am Acad Dermatol 2009

M Potrony et al.
J Am Acad Dermatol 2014

S Puig et al.
Genet Med 2016

E Gillanders et al.
Am J Hum Genet 2003

LA Cannon-Albright et al.
J Invest Dermatol 2013

V Hoiom et al.
Genes Chromosomes Cancer 2011

KF Kerstann et al.
Cancer Epidemiol Biomarkers Prev 2008

A Thomas et al.
Stat Comput 2000

Similar Publications