Ultradeep targeted sequencing reveals low allele frequencies of somatic JAK2 and MPL variants in patients with abdominal vein thromboses: results of an ongoing prospective prevalence study in Mecklenburg-West Pomerania

• Main Authors: Luise Grunwald, Christina Grosse-Thie, Sina Sender, Gudrun Knuebel, Saskia Krohn, Catrin Roolf, Christian Junghanss, Larissa Henze, Hugo Murua Escobar
• Format: Article
• Language: English
• Published: BMC 2020-12-01
• Series: Biomarker Research
• Subjects: Molecular genetics; Blood coagulation; Myeloproliferative neoplasms; Splanchnic vein thrombosis; Next generation sequencing; Ultradeep targeted sequencing
• Online Access: https://doi.org/10.1186/s40364-020-00254-9
• ISSN: 2050-7771

Abstract Myeloproliferative neoplasms are characterized by mutations in JAK2, MPL and CALR genes. Commonly in diagnostics and previous studies mainly sequencing and common PCR techniques under conventional detection limits are used. Splanchnic vein thromboses are rare, but often appear associated with myeloproliferative neoplasms and represent serious complications. Herein, blood from patients with abdominal vein thromboses in Mecklenburg-West Pomerania (federal district of northern Germany), included in an ongoing prospective prevalence study, was analyzed by next generation sequencing representing the complete protein coding regions of JAK2, MPL and CALR genes with a coverage of > 2000 reads, therefore an ultradeep targeting approach. JAK2 V617F mutations were detected in 11/44 patients. In four of these cases allele frequencies ranged below the conventional cut off of 2%. MPL W515R was detected in 3/44 cases in low frequencies. Very low allele frequencies of JAK2 and MPL variants in patients with abdominal vein thromboses may indicate early manifestations of myeloproliferative neoplasms.