Informace o publikaci

A deep intronic recurrent CHEK2 variant c.1009-118_1009-87delinsC affects pre-mRNA splicing and contributes to hereditary breast cancer predisposition

Autoři	ZEMANKOVA Petra CERNA Marta HORACKOVA Klara ERNST Corinna SOUKUPOVA Jana BORECKA Marianna BLUEMCKE Britta CERNA Leona CERNA Monika CURTISOVA Vaclava DOLEZALOVA Tatana DUSKOVA Petra DVORAKOVA Lenka FORETOVÁ Lenka HAVRANEK Ondrej HAUKE Jan HAHNEN Eric HODULOVA Miloslava HOVHANNISYAN Milena HRUSKOVA Lucie JANATOVA Marketa JANIKOVA Maria JELINKOVA Sandra JUST Pavel KOSAROVA Marcela KOUDOVA Monika KRUTILKOVA Vera MACHACKOVA Eva MATEJKOVA Katerina MICHALOVSKA Renata MIŠOVE Adéla NEHASIL Petr NEMCOVA Barbora NOVOTNY Jan PANCZAK Ales PESEK Pavel SCHEINOST Ondrej SPRINGER Drahomira STASTNA Barbora STRANECKY Viktor SUBRT Ivan TAVANDZIS Spiros TURECKOVA Eva VESELA Kamila VLCKOVA Zdenka VOCKA Michal WAPPENSCHMIDT Barbara ZIMA Tomas KLEIBL Zdenek KLEIBLOVA Petra
Rok publikování	2024
Druh	Článek v odborném periodiku
Časopis / Zdroj	BREAST
Citace
Doi	https://doi.org/10.1016/j.breast.2024.103721
Klíčová slova	Deep intronic CHEK2 variant; Breast cancer; NGS; RNA analysis; Genetic testing
Popis	Germline CHEK2 pathogenic variants confer an increased risk of female breast cancer (FBC). Here we describe a recurrent germline intronic variant c.1009-118_1009-87delinsC, which showed a splice acceptor shift in RNA analysis, introducing a premature stop codon (p.Tyr337PhefsTer37). The variant was found in 21/10,204 (0.21%) Czech FBC patients compared to 1/3250 (0.03%) controls (p = 0.04) and in 4/3639 (0.11%) FBC patients from an independent German dataset. In addition, we found this variant in 5/2966 (0.17%) Czech (but none of the 443 German) ovarian cancer patients, three of whom developed early-onset tumors. Based on these observations, we classified this variant as likely pathogenic.