Inherited and acquired variations in the hyaluronan synthase 1 (HAS1) gene may contribute to disease progression in multiple myeloma and Waldenstrom macroglobulinemia
| Autor: | Steven P. Treon, Michael J. Mant, Tony Reiman, Jitra Kriangkum, Jennifer Hodges, Hemalatha Kuppusamy, Sophia Adamia, Linda M. Pilarski, Patrick M. Pilarski, Andrew R. Belch, Anirban Ghosh, Amanda A. Reichert |
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| Rok vydání: | 2008 |
| Předmět: |
Somatic cell
Chronic lymphocytic leukemia Hematopoietic System RNA Splicing Immunology Biology medicine.disease_cause Biochemistry Exon medicine Humans Glucuronosyltransferase Mutation Base Sequence Intron Waldenstrom macroglobulinemia Genetic Variation Cell Biology Hematology Exons medicine.disease Introns Hyaluronan synthase RNA splicing biology.protein Cancer research Disease Progression Waldenstrom Macroglobulinemia Multiple Myeloma Hyaluronan Synthases |
| Zdroj: | Blood. 112(13) |
| ISSN: | 1528-0020 |
| Popis: | To characterize genetic contributions toward aberrant splicing of the hyaluronan synthase 1 (HAS1) gene in multiple myeloma (MM) and Waldenstrom macroglobulinemia (WM), we sequenced 3616 bp in HAS1 exons and introns involved in aberrant splicing, from 17 patients. We identified a total of 197 HAS1 genetic variations (GVs), a range of 3 to 24 GVs/patient, including 87 somatic GVs acquired in splicing regions of HAS1. Nearly all newly identified inherited and somatic GVs in MM and/or WM were absent from B chronic lymphocytic leukemia, nonmalignant disease, and healthy donors. Somatic HAS1 GVs recurred in all hematopoietic cells tested, including normal CD34+ hematopoietic progenitor cells and T cells, or as tumor-specific GVs restricted to malignant B and plasma cells. An in vitro splicing assay confirmed that HAS1 GVs direct aberrant HAS1 intronic splicing. Recurrent somatic GVs may be enriched by strong mutational selection leading to MM and/or WM. |
| Databáze: | OpenAIRE |
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