A germline exome analysis reveals harmful POT1 variants in multiple myeloma patients and families

eJHaem

article

Marja Hakkarainen¹  Jessica R. Koski¹  Caroline A. Heckman⁴  Pekka Anttila³  Raija Silvennoinen³  Juha Lievonen³  Outi Kilpivaara¹  Ulla Wartiovaara-Kautto¹ 

[1] Applied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki;Department of Medical and Clinical Genetics/Medium, Faculty of Medicine, University of Helsinki;Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki;Institute for Molecular Medicine Finland - FIMM, HiLIFE - Helsinki institute of Life Science, University of Helsinki;iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki;HUS Diagnostic Center ,(Helsinki University Hospital), HUSLAB Laboratory of Genetics;Outi Kilpivaara and Ulla Wartiovaara-Kautto contributed equally to this work.

关键词: genetic analysis;    multiple myeloma;    germline mutations;   

DOI  :  10.1002/jha2.557

来源: Wiley

【 摘 要 】

Observations of inherited susceptibility to multiple myeloma have led to active research in defining predisposing genes to the disease. Here, we analysed 128 plasma cell dyscrasia patients’ germline whole-exome sequencing data. Rare dominantly inherited pathogenic or likely pathogenic (P/LP) variant was found in 9.4% of the patients. Among the P/LP variants, CHEK2 ( p. Thr410MetfsTer15) was the most prevalent ( n = 5, 3.9%). Interestingly, P/LP variants in POT1 were identified in three patients (2.3%). Our findings broaden the spectrum of  POT1 -related cancers and demonstrate the importance of the germline genetic analysis in hematological malignancies.

【 授权许可】

Unknown