Concurrent pathogenic variations in patients with hereditary cancer syndromes
European Journal of Medical Genetics, cilt.64, sa.12, 2021 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 64 Sayı: 12
- Basım Tarihi: 2021
- Doi Numarası: 10.1016/j.ejmg.2021.104366
- Dergi Adı: European Journal of Medical Genetics
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, MEDLINE
- Anahtar Kelimeler: Next generation sequencing, Hereditary cancer, Concurrent variations, Double heterozygous
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Cancer is a multifactorial disorder; however, 5–10% of all cancers show hereditary background. In recent years many targeted next generation sequencing panels comprising cancer predisposition genes have been developed and used for diagnostic purposes in patients with increased cancer risk. Screening multiple genes at a time allows multiple variants in different genes to be detected as well. This study aims to determine the cases with concurrent mutations in different hereditary cancer predisposition genes and how they are clinically affected. Here, we screened 1090 index cases by next generation sequencing based hereditary cancer panels and evaluated the reflection of multiple variations on the phenotype. We detected 11 (1%) cases with pathogenic variants in more than one gene. These concurrent variations occurred mostly in BRCA1/2 (7/11) accompanied with MUTYH, ATM, CHECK2, NBN, and RAD50. In addition, MUTYH&ATM, NBN&MSH6, MUTYH&CHEK2 double heterozygous cases were detected. Moreover, we identified a case with three heterozygous variations in CDH1, MUTYH, and CHEK2. These patients presented malignancies that were mostly related to pathogenic variations they carried. Although they are rare, defining double heterozygous cases is important for managing appropriate therapy and accurate genetic consulting for the patients and family members.