Somatic Mutational Landscape of Hereditary Hematopoietic Malignancies Associated with Germline Variants in RUNX1, GATA2 and DDX41

Diagnosing familial platelet disorder with predisposition to myeloid malignancy: Lessons learned from a germline whole‐gene deletion of RUNX1

“…In germline RUNX1 carriers, CH is more prevalent and has an earlier age of onset. 10 CH is present in approximately one-third of germline RUNX1 carriers before they develop malignancy and the persistence of clonal variants in RUNX1-driven malignancy implies CH is a direct precursor to cancer in these individuals. 10 Secondly, initial diagnostic workup frequently includes molecular characterization by NGS.…”

“…10 CH is present in approximately one-third of germline RUNX1 carriers before they develop malignancy and the persistence of clonal variants in RUNX1-driven malignancy implies CH is a direct precursor to cancer in these individuals. 10 Secondly, initial diagnostic workup frequently includes molecular characterization by NGS. However, gene panels often target somatic (not germline) variants and conventional short-read NGS is designed to identify single-nucleotide variants (SNVs) and small insertion/deletion variants, limiting the detection of large copy number variants (CNVs).…”