Germline variants in DNA repair genes, including BRCA1/2, may cause familial myeloproliferative neoplasms.

ABSTRACT: The molecular causes of myeloproliferative neoplasms (MPNs) have not yet been fully elucidated. Approximately 7% to 8% of the patients carry predisposing genetic germline variants that lead to driver mutations, which enhance JAK-STAT signaling. To identify additional predisposing genetic germline variants, we performed whole-exome sequencing in 5 families, each with parent-child or sibling pairs affected by MPNs and carrying the somatic JAK2 V617F mutation. In 4 families, we detected rare germline variants in known tumor predisposition genes of the DNA repair pathway, including the highly penetrant BRCA1 and BRCA2 genes. The identification of an underlying hereditary tumor predisposition is of major relevance for the individual patients as well as for their families in the context of thera

SUBMITTER: Elbracht M 

PROVIDER: S-EPMC8525218 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature