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

被引：21

作者：

Adamia, Sophia ^{[1
]}

Reichert, Amanda A. ^{[1
]}

Kuppusamy, Hemalatha ^{[1
]}

Kriangkum, Jitra ^{[1
]}

Ghosh, Anirban ^{[1
]}

Hodges, Jennifer J. ^{[1
]}

Pilarski, Patrick M. ^{[2
]}

Treon, Steven P. ^{[3
]}

Mant, Michael J. ^{[4
]}

Reiman, Tony ^{[1
]}

Belch, Andrew R. ^{[1
]}

Pilarski, Linda M. ^{[1
]}

机构：

[1] Univ Alberta, Cross Canc Inst, Dept Oncol, Edmonton, AB T6G 1Z2, Canada

[2] Univ Alberta, Cross Canc Inst, Dept Elect & Comp Engn, Edmonton, AB T6G 1Z2, Canada

[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[4] Univ Alberta, Cross Canc Inst, Dept Med, Edmonton, AB T6G 1Z2, Canada

来源：

BLOOD | 2008年 / 112卷 / 13期

关键词：

D O I：

10.1182/blood-2008-02-141770

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (Blood. 2008; 112: 5111-5121)

引用

页码：5111 / 5121

页数：11

共 64 条

[1] Potential impact of a single nucleotide polymorphism in the hyaluronan synthase 1 gene in Waldenstrom's macroglobulinemia [J].

Adamia, S ;

Treon, SP ;

Reiman, T ;

Tournilhac, O ;

McQuarrie, C ;

Mant, MJ ;

Belch, AR ;

Pilarski, LM .

CLINICAL LYMPHOMA, 2005, 5 (04) :253-256

[2] Intronic splicing of hyaluronan synthase 1 (HAS1):: a biologically relevant indicator of poor outcome in multiple myeloma [J].

Adamia, S ;

Reiman, T ;

Crainie, M ;

Mant, MJ ;

Belch, AR ;

Pilarski, LM .

BLOOD, 2005, 105 (12) :4836-4844

[3] Abnormal expression of hyaluronan synthases in patients with Waldenstrom's macroglobulimenia [J].

Adamia, S ;

Crainie, M ;

Kriangkum, J ;

Mant, MJ ;

Belch, AR ;

Pilarski, LM .

SEMINARS IN ONCOLOGY, 2003, 30 (02) :165-168

[4] Different splicing defects lead to differential effects downstream of the lipid and protein phosphatase activities of PTEN [J].

Agrawal, S ;

Pilarski, R ;

Eng, C .

HUMAN MOLECULAR GENETICS, 2005, 14 (16) :2459-2468

[5] Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell [J].

Bonnet, D ;

Dick, JE .

NATURE MEDICINE, 1997, 3 (07) :730-737

[6] Heregulin-mediated ErbB2-ERK signaling activates hyaluronan synthases leading to CD44-dependent ovarian tumor cell growth and migration [J].

Bourguignon, Lilly Y. W. ;

Gilad, Eli ;

Peyrollier, Karine .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (27) :19426-19441

[7] p53 intronic point mutation, aberrant splicing and telomeric associations in a case of B-chronic lymphocytic leukaemia [J].

Bromidge, T ;

Lowe, C ;

Prentice, A ;

Johnson, S .

BRITISH JOURNAL OF HAEMATOLOGY, 2000, 111 (01) :223-229

[8] Defective splicing, disease and therapy: searching for master checkpoints in exon definition [J].

Buratti, Emanuele ;

Baralle, Marco ;

Baralle, Francisco E. .

NUCLEIC ACIDS RESEARCH, 2006, 34 (12) :3494-3510

[9] Intron retention and frameshift mutations result in severe pyruvate carboxylase deficiency in two male siblings [J].

Carbone, MA ;

Applegarth, DA ;

Robinson, BH .

HUMAN MUTATION, 2002, 20 (01) :48-56

[10] Listening to silence and understanding nonsense: Exonic mutations that affect splicing [J].

Cartegni, L ;

Chew, SL ;

Krainer, AR .

NATURE REVIEWS GENETICS, 2002, 3 (04) :285-298

← 1 2 3 4 5 6 7 →