Abstract | BACKGROUND: METHODS: Between January, 2005, and February, 2009, serum and peripheral blood cells were obtained from consecutive patients with MGUS or multiple myeloma and healthy blood donors, and paratarg-7 was analysed by DNA sequencing, SDS-PAGE, isoelectric focusing, and western blotting. FINDINGS: Mutations or polymorphisms of paratarg-7 were not noted, but hyperphosphorylation was detected in 35 (13.9%) of 252 patients with MGUS or multiple myeloma, all of whom had an anti-paratarg-7-specific paraprotein. Analysis of eight families showed that hyperphosphorylated paratarg-7 is inherited in a dominant fashion, and that carriers of hyperphosphorylated paratarg-7 have an increased risk of developing MGUS and multiple myeloma (odds ratio [OR] 7.9, 95% CI 2.8-22.6; p=0.0001). INTERPRETATION: Familial MGUS and multiple myeloma were associated with a dominant inheritance of hyperphosphorylated paratarg-7, enabling family members at increased risk for MGUS or multiple myeloma to be identified. That only patients with MGUS or multiple myeloma who are carriers of hyperphosphorylated paratarg-7 had a paratarg-7-specific paraprotein suggests that the hyperphosphorylation of paratarg-7 induces auto-immunity and is involved in the pathogenesis of MGUS and multiple myeloma; for example, by chronic antigenic stimulation. FUNDING: Förderverein Krebsforschung Saar-Pfalz-Mosel e.V. (eingetragener Verein: officially registered charity) and HOMFOR (the research programme of the Saarland University Faculty of Medicine).
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Authors | Sandra Grass, Klaus-Dieter Preuss, Manfred Ahlgrimm, Natalie Fadle, Evi Regitz, Claudia Pfoehler, Niels Murawski, Michael Pfreundschuh |
Journal | The Lancet. Oncology
(Lancet Oncol)
Vol. 10
Issue 10
Pg. 950-6
(Oct 2009)
ISSN: 1474-5488 [Electronic] England |
PMID | 19767238
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Blood Proteins
- Membrane Proteins
- Paraproteins
- STOML2 protein, human
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Topics |
- Adult
- Aged
- Blood Proteins
(physiology)
- Case-Control Studies
- Child
- Female
- Genes, Dominant
- Humans
- Male
- Membrane Proteins
(physiology)
- Middle Aged
- Monoclonal Gammopathy of Undetermined Significance
(genetics, metabolism, pathology)
- Multiple Myeloma
(genetics, metabolism, pathology)
- Paraproteins
(physiology)
- Pedigree
- Phosphorylation
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