Identification of Germline Mutations in Melanoma Patients with Early Onset, Double Primary Tumors, or Family Cancer History by NGS Analysis of 217 Genes
Identifikátory výsledku
Kód výsledku v 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>
Nalezeny alternativní kódy
RIV/00216208:11110/20:10417726 RIV/00209805:_____/20:00078496 RIV/00064165:_____/20:10417726
Výsledek na webu
<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>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Identification of Germline Mutations in Melanoma Patients with Early Onset, Double Primary Tumors, or Family Cancer History by NGS Analysis of 217 Genes
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
Identification of Germline Mutations in Melanoma Patients with Early Onset, Double Primary Tumors, or Family Cancer History by NGS Analysis of 217 Genes
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30204 - Oncology
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
BIOMEDICINES
ISSN
2227-9059
e-ISSN
—
Svazek periodika
8
Číslo periodika v rámci svazku
10
Stát vydavatele periodika
CH - Švýcarská konfederace
Počet stran výsledku
18
Strana od-do
404
Kód UT WoS článku
000584522600001
EID výsledku v databázi Scopus
—