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Monitoring multiple myeloma by quantification of recurrent mutations in serum.
Rustad, Even Holth; Coward, Eivind; Skytøen, Emilie R; Misund, Kristine; Holien, Toril; Standal, Therese; Børset, Magne; Beisvag, Vidar; Myklebost, Ola; Meza-Zepeda, Leonardo A; Dai, Hong Yan; Sundan, Anders; Waage, Anders.
Afiliación
  • Rustad EH; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
  • Coward E; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
  • Skytøen ER; Norwegian Cancer Genomics Consortium, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
  • Misund K; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
  • Holien T; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
  • Standal T; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
  • Børset M; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
  • Beisvag V; CEMIR - Center for Molecular Inflammation Research, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
  • Myklebost O; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
  • Meza-Zepeda LA; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
  • Dai HY; Norwegian Cancer Genomics Consortium, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
  • Sundan A; Institute for Clinical Science, University of Bergen, Trondheim, Norway.
  • Waage A; Institute for Cancer Research, Oslo University Hospital, Trondheim, Norway.
Haematologica ; 102(7): 1266-1272, 2017 07.
Article en En | MEDLINE | ID: mdl-28385781
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<0.002). There was a striking covariation between circulating mutation levels and M protein in ten out of 11 patients with sequential samples. When relapse evaluation by circulating tumor DNA and M protein could be directly compared, the circulating tumor DNA showed relapse earlier in two patients (3 and 9 months), later in one patient (4 months) and in three patients there was no difference. In three patients with transformation to aggressive disease, the concentrations of mutations in serum increased up to 400 times, an increase that was not seen for the M protein. In conclusion, circulating tumor DNA in myeloma is a multi-faceted biomarker reflecting mutated cells, total tumor mass and transformation to a more aggressive disease. Its properties are both similar and complementary to M protein.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN de Neoplasias / Biomarcadores de Tumor / Ácidos Nucleicos Libres de Células / Mieloma Múltiple / Mutación Tipo de estudio: Diagnostic_studies / Observational_studies / Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Haematologica Año: 2017 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Italia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN de Neoplasias / Biomarcadores de Tumor / Ácidos Nucleicos Libres de Células / Mieloma Múltiple / Mutación Tipo de estudio: Diagnostic_studies / Observational_studies / Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Haematologica Año: 2017 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Italia