Gene expression and single nucleotide polymorphism array analyses of spindle cell lipomas and conventional lipomas with 13q14 deletion

Genes Chromosomes and Cancer - Tập 50 Số 8 - Trang 619-632 - 2011
Hammurabi Bartuma1, Karolin H. Nord1, Gemma Macchia1,2, Malin Isaksson1, Jenny Nilsson1, Henryk A. Domanski3, Nils Mandahl1, Fredrik Mertens1
1Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden
2Department of Genetics and Microbiology, University of Bari, Bari, Italy
3Department of Pathology, University and Regional Laboratories, Skåne University Hospital, Lund, Sweden

Tóm tắt

AbstractSpindle cell lipomas (SCL) are circumscribed, usually s.c. tumors that typically occur on the posterior neck, shoulder, and back of middle aged men. Cytogenetically, almost all SCL are characterized by deletions of chromosome arm 13q, often in combination with loss of 16q. Deletions of 13q are seen also in approximately 15% of conventional lipomas. Through single nucleotide polymorphism (SNP) array analyses, we identified two minimal deleted regions (MDR) in 13q14 in SCL. In MDR1, four genes were located, including the tumor suppressor gene RB1. MDR1 in SCL overlapped with the MDR detected in conventional lipomas with 13q14 deletion. In MDR2 in SCL there were 34 genes and the two microRNA (miRNA) genes miR‐15a and miR‐16‐1. Global gene expression analysis was used to study the impact of the deletions on genes mapping to the two SCL‐associated MDR. Five genes (C13orf1, DHRS12, ATP7B, ALG11, and VPS36) in SCL and one gene (C13orf1) in conventional lipomas with 13q‐deletions were found to be significantly underexpressed compared with control tissues. Quantitative real‐time PCR showed that miR‐16‐1 was expressed at lower levels in SCL than in the control samples. No mutations were found at sequencing of RB1, miR‐15a, and miR‐16‐1. Our findings further delineate the target region for the 13q deletion in SCL and conventional lipomas and show that the deletions are associated with down‐regulated expression of several genes, notably C13orf1, which was the only gene to be significantly down‐regulated in both tumor types. © 2011 Wiley‐Liss, Inc.

Từ khóa


Tài liệu tham khảo

10.1016/0092-8674(95)90052-7

10.1007/BF00210629

10.1158/0008-5472.CAN-08-4277

10.1002/gcc.20445

10.1186/1476-4598-8-36

10.1038/nm.1880

10.1073/pnas.242606799

10.1056/NEJMoa050995

10.1038/nature09264

10.1101/gad.10.21.2794

10.1073/pnas.190343597

10.1016/j.leukres.2009.10.026

10.1002/ijc.10864

10.1097/01.MP.0000092954.42656.94

10.1074/jbc.M109.034280

10.1016/S1534-5807(02)00360-X

10.1016/S1534-5807(02)00190-9

Fletcher CDM, 1996, Correlation between clinicopathological features and karyotype in lipomatous tumors. A report of 178 cases from the Chromosomes and Morphology (CHAMP) Collaborative Study Group, Am J Pathol, 148, 623

Fletcher CDM, 2002, World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone, 31

10.1038/323643a0

10.1038/sj.ejhg.5200694

10.1074/jbc.274.4.2386

10.1038/ng1416

ISCN, 2009, An International System for Human Cytogenetic Nomenclature 2009, 138

10.1042/BC20080213

10.1016/j.ccr.2009.11.019

La Starza R, 1998, Molecular delineation of 13q deletion boundaries in 20 patients with myeloid malignancies, Blood, 91, 231, 10.1182/blood.V91.1.231

10.1093/jnci/89.1.83

10.1086/427565

10.1006/meth.2001.1262

Mabuchi H, 2001, Cloning and characterization of CLLD6, CLLD7, and CLLD8, novel candidate genes for leukemogenesis at chromosome 13q14, a region commonly deleted in B‐cell chronic lymphocytic leukemia, Cancer Res, 61, 2870

10.1007/BF00366238

10.1002/gcc.2870090309

10.1007/BF01194267

10.1038/nature02873

10.1182/blood.V99.11.4116

Mitelman F, 2011, Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer

10.1016/S1470-2045(10)70066-8

10.1101/gad.974702

10.1002/1097-0029(20001201)51:5<456::AID-JEMT8>3.0.CO;2-H

10.1182/blood-2009-10-249367

10.1093/hmg/ddq016

10.1182/blood-2009-01-198408

Schlade‐Bartusiak K, 2005, Significant involvement of chromosome 13q deletions in progression of larynx cancer, detected by comparative genomic hybridization, J Appl Genet, 46, 407

10.1038/ng0895-436

10.1186/gb-2008-9-9-r136

10.1186/1471-2105-9-409

10.1111/j.1349-7006.2007.00608.x

10.1016/S0165-4608(03)00126-2

10.1016/0092-8674(95)90385-2

10.1073/pnas.0508889103

Zojer N, 2000, Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization, Blood, 95, 1925, 10.1182/blood.V95.6.1925

Thông tin
Thông tin xuất bản

Genes Chromosomes and Cancer

Tập 50 Số 8

619-632

Thông tin tác giả