JAK2 V617F mutation in plasma cell-free DNA preceding clinically overt myelofibrosis: Implications for early diagnosis. Cancer Biol Ther 2018 Aug 03;19(8):664-668
Date
03/23/2018Pubmed ID
29565699Pubmed Central ID
PMC6067874DOI
10.1080/15384047.2018.1450120Scopus ID
2-s2.0-85050400905 (requires institutional sign-in at Scopus site)Abstract
A 52 year-old man with Erdheim-Chester Disease (ECD) (a non-Langerhans polyostotic sclerosing histiocytosis) had next-generation sequencing (NGS) performed as part of his diagnostic workup. In addition to the tissue BRAF V600E mutation that is found in over 50% of ECD cases, he was also found to have a JAK2 V617F alteration in cell-free circulating tumor DNA (ctDNA) (liquid biopsy). The latter was thought to be an "incidental" finding, perhaps due to clonal hematopoiesis (though this usually occurs in older individuals), as his blood counts were normal and he had no splenomegaly. Approximately 13 months after the ctDNA test showing JAK2 V617F, he developed anemia, thrombocytopenia, and splenomegaly. Marrow biopsy then showed megakaryocytic atypia and markedly increased marrow fibrosis, consistent with WHO grade 2 of 3 myelofibrosis. Therefore, the patient was determined to have ECD with a typical BRAF V600E mutation, as well as primary myelofibrosis, with the latter diagnosis manifesting clinically over one year after the JAK2 V617F was first detected in ctDNA. He recently was started on the JAK2 inhibitor ruxolitinib. This case demonstrates that genomic alterations detected by liquid biopsy for evaluation of specific malignancies already present may serve as an early harbinger of hematological disease.
Author List
Choi MY, Kato S, Wang HY, Lin JH, Lanman RB, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SubstitutionBiomarkers
Biopsy
Bone Marrow
Cell-Free Nucleic Acids
Codon
Early Diagnosis
Humans
Janus Kinase 2
Male
Middle Aged
Mutation
Primary Myelofibrosis
