Inherited and acquired variations in the hyaluronan synthase 1 (HAS1) gene may contribute to disease progression in multiple myeloma and Waldenstrom macroglobulinemia.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Adamia S,Reichert AA,Kuppusamy H,Kriangkum J,Ghosh A,Hodges JJ,Pilarski PM,Treon SP,Mant MJ,Reiman T,Belch AR,Pilarski LM

doi

10.1182/blood-2008-02-141770

subject

Has Abstract

pub_date

2008-12-15 00:00:00

pages

5111-21

issue

13

eissn

0006-4971

issn

1528-0020

pii

blood-2008-02-141770

journal_volume

112

pub_type

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