Identification of Germline Mutations in Melanoma Patients with Early Onset, Double Primary Tumors, or Family Cancer History by NGS Analysis of 217 Genes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F20%3A00539741" target="_blank" >RIV/68378050:_____/20:00539741 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/20:10417726 RIV/00209805:_____/20:00078496 RIV/00064165:_____/20:10417726

Result on the web

<a href="https://www.mdpi.com/2227-9059/8/10/404" target="_blank" >https://www.mdpi.com/2227-9059/8/10/404</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/biomedicines8100404" target="_blank" >10.3390/biomedicines8100404</a>

Result language

angličtina

Original language name

Identification of Germline Mutations in Melanoma Patients with Early Onset, Double Primary Tumors, or Family Cancer History by NGS Analysis of 217 Genes

Original language description

Cutaneous melanoma is the deadliest skin malignity with a rising prevalence worldwide. Patients carrying germline mutations in melanoma-susceptibility genes face an increased risk of melanoma and other cancers. To assess the spectrum of germline variants, we analyzed 264 Czech melanoma patients indicated for testing due to early melanoma (at <25 years) or the presence of multiple primary melanoma/melanoma and other cancer in their personal and/or family history. All patients were analyzed by panel next-generation sequencing targeting 217 genes in four groups: high-to-moderate melanoma risk genes, low melanoma risk genes, cancer syndrome genes, and other genes with an uncertain melanoma risk. Population frequencies were assessed in 1479 population-matched controls. Selected POT1 and CHEK2 variants were characterized by functional assays. Mutations in clinically relevant genes were significantly more frequent in melanoma patients than in controls (31/264, 11.7% vs. 58/1479, 3.9%, p = 2.0 x 10(-6)). A total of 9 patients (3.4%) carried mutations in high-to-moderate melanoma risk genes (CDKN2A, POT1, ACD) and 22 (8.3%) patients in other cancer syndrome genes (NBN, BRCA1/2, CHEK2, ATM, WRN, RB1). Mutations in high-to-moderate melanoma risk genes (OR = 52.2, 95%CI 6.6-413.1, p = 3.2 x 10(-7)) and in other cancer syndrome genes (OR = 2.3, 95%CI 1.4-3.8, p = 0.003) were significantly associated with melanoma risk. We found an increased potential to carry these mutations (OR = 2.9, 95%CI 1.2-6.8) in patients with double primary melanoma, melanoma and other primary cancer, but not in patients with early age at onset. The analysis revealed affected genes in Czech melanoma patients and identified individuals who may benefit from genetic testing and future surveillance management of mutation carriers.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30204 - Oncology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

BIOMEDICINES

ISSN

2227-9059

e-ISSN

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Volume of the periodical

8

Issue of the periodical within the volume

10

Country of publishing house

CH - SWITZERLAND

Number of pages

18

Pages from-to

404

UT code for WoS article

000584522600001

EID of the result in the Scopus database

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