POT1 germline mutations but not TERT promoter mutations are implicated in melanoma susceptibility in a large cohort of Spanish melanoma families.
Br J Dermatol
; 181(1): 105-113, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-30451293
ABSTRACT
BACKGROUND:
Germline mutations in telomere-related genes such as POT1 and TERT predispose individuals to familial melanoma.OBJECTIVES:
To evaluate the prevalence of germline mutations in POT1 and TERT in a large cohort of Spanish melanoma-prone families (at least two affected first- or second-degree relatives).METHODS:
Overall, 228 CDKN2A wild-type melanoma-prone families were included in the study. Screening of POT1 was performed in one affected person from each family and TERT was sequenced in one affected patient from 202 families (26 families were excluded owing to DNA exhaustion/degradation). TERT promoter sequencing was extended to an additional 30 families with CDKN2A mutation and 70 patients with sporadic multiple primary melanoma (MPM) with a family history of other cancers.RESULTS:
We identified four families with potentially pathogenic POT1 germline mutations a missense variant c.233T>C (p.Ile78Thr); a nonsense variant c.1030G>T (p.Glu344*); and two other variants, c.255G>A (r.125_255del) and c.1792G>A (r.1791_1792insAGTA, p.Asp598Serfs*22), which we confirmed disrupted POT1 mRNA splicing. A TERT promoter variant of unknown significance (c.-125C>A) was detected in a patient with MPM, but no germline mutations were detected in TERT promoter in cases of familial melanoma.CONCLUSIONS:
Overall, 1·7% of our CDKN2A/CDK4-wild type Spanish melanoma-prone families carry probably damaging mutations in POT1. The frequency of TERT promoter germline mutations in families with melanoma in our population is extremely rare.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Regiões Promotoras Genéticas
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Telomerase
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Predisposição Genética para Doença
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Proteínas de Ligação a Telômeros
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Melanoma
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
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Female
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Humans
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Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Br J Dermatol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Espanha