Monitoring multiple myeloma by quantification of recurrent mutations in serum
Even Holth Rustad,
Eivind Coward,
Emilie R Skytøen,
Kristine Misund,
Toril Holien,
Therese Standal,
Magne Børset,
Vidar Beisvag,
Ola Myklebost,
Leonardo A Meza-Zepeda,
Hong Yan Dai,
Anders Sundan,
Anders Waage
Affiliations
Even Holth Rustad
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
Eivind Coward
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway;Norwegian Cancer Genomics Consortium, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
Emilie R Skytøen
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
Kristine Misund
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
Toril Holien
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
Therese Standal
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway;CEMIR – Center for Molecular Inflammation Research, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
Magne Børset
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
Vidar Beisvag
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
Ola Myklebost
Norwegian Cancer Genomics Consortium, Norwegian University of Science and Technology, NTNU, Trondheim, Norway;Institute for Clinical Science, University of Bergen, Trondheim, Norway;Institute for Cancer Research, Oslo University Hospital, Trondheim, Norway
Leonardo A Meza-Zepeda
Norwegian Cancer Genomics Consortium, Norwegian University of Science and Technology, NTNU, Trondheim, Norway;Institute for Cancer Research, Oslo University Hospital, Trondheim, Norway
Hong Yan Dai
Department of Pathology and Medical Genetics, St. Olav’s University Hospital, Trondheim, Norway
Anders Sundan
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway;CEMIR – Center for Molecular Inflammation Research, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
Anders Waage
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway;Norwegian Cancer Genomics Consortium, Norwegian University of Science and Technology, NTNU, Trondheim, Norway;Department of Hematology, St. Olav’s University Hospital, Trondheim, Norway
Circulating tumor DNA is a promising biomarker to monitor tumor load and genome alterations. We explored the presence of circulating tumor DNA in multiple myeloma patients and its relation to disease activity during long-term follow-up. We used digital droplet polymerase chain reaction analysis to monitor recurrent mutations, mainly in mitogen activated protein kinase pathway genes NRAS, KRAS and BRAF. Mutations were identified by next-generation sequencing or polymerase chain reaction analysis of bone marrow plasma cells, and their presence analyzed in 251 archived serum samples obtained from 20 patients during a period of up to 7 years. In 17 of 18 patients, mutations identified in bone marrow during active disease were also found in a time-matched serum sample. The concentration of mutated alleles in serum correlated with the fraction in bone marrow plasma cells (r=0.507, n=34, P
