Identification of chromosomal aberrations associated with disease progression and a novel 3q13.31 deletion involving LSAMP gene in osteosarcoma

被引：43

作者：

Yen, Chueh-Chuan ^{[1
,2
,3
,10
]}

Chen, Wei-Ming ^{[4
,10
]}

Chen, Tain-Hsiung ^{[4
,10
]}

Chen, Winby York-Kwan ^{[5
,16
]}

Chen, Paul Chih-Hsueh ^{[5
]}

Chiou, Hong-Jen ^{[6
,10
]}

Hung, Giun-Yi ^{[7
,10
]}

Wu, Hung-Ta Hondar ^{[6
,10
]}

Wei, Chao-Jung ^{[6
,10
]}

Shiau, Cheng-Ying ^{[8
,10
]}

Wu, Yu-Chung ^{[9
,10
]}

Chao, Ta-Chung ^{[2
,3
,10
]}

Tzeng, Cheng-Hwai ^{[2
,3
,10
]}

Chen, Po-Min ^{[2
,3
,10
]}

Lin, Chi-Hung ^{[9
,11
,12
,17
]}

Chen, Yann-Jang ^{[13
,14
,15
,17
]}

Fletcher, Jonathan A. ^{[1
]}

机构：

[1] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[2] Taipei Vet Gen Hosp, Genom Res Ctr, Taipei, Taiwan

[3] Taipei Vet Gen Hosp, Div Hematol & Oncol, Dept Med, Taipei, Taiwan

[4] Taipei Vet Gen Hosp, Dept Orthoped, Taipei, Taiwan

[5] Taipei Vet Gen Hosp, Dept Pathol, Taipei, Taiwan

[6] Taipei Vet Gen Hosp, Dept Radiol, Taipei, Taiwan

[7] Taipei Vet Gen Hosp, Dept Pediat, Taipei, Taiwan

[8] Taipei Vet Gen Hosp, Ctr Canc, Taipei, Taiwan

[9] Taipei Vet Gen Hosp, Dept Surg, Taipei, Taiwan

[10] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan

[11] Natl Yang Ming Univ, Inst Microbiol & Immunol, Taipei 112, Taiwan

[12] Natl Yang Ming Univ, Inst Microbiol & Immunol, Taipei 112, Taiwan

[13] Natl Yang Ming Univ, Fac Life Sci, Taipei 112, Taiwan

[14] Natl Yang Ming Univ, Inst Genome Sci, Taipei 112, Taiwan

[15] Natl Yang Ming Univ, Inst Clin Med, Taipei 112, Taiwan

[16] Taipei Inst Pathol, Taipei, Taiwan

[17] Taipei City Hosp, Taipei 103, Taiwan

来源：

INTERNATIONAL JOURNAL OF ONCOLOGY | 2009年 / 35卷 / 04期

关键词：

limbic system-associated membrane protein; oligonucleotide arrays; osteosarcoma; real-time quantitative PCR; single-nucleotide polymorphism; tumor suppressor gene; COMPARATIVE GENOMIC HYBRIDIZATION; ALLELIC IMBALANCE ANALYSIS; LOSS-OF-HETEROZYGOSITY; IN-SITU HYBRIDIZATION; UNIPARENTAL DISOMY; COPY NUMBER; SNP-ARRAY; KIT GENE; AMPLIFICATIONS; OVEREXPRESSION;

D O I：

10.3892/ijo_00000390

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Five osteosarcoma (OS) cell lines, 37 OS tumors and 9 corresponding non-neoplastic samples were genotyped by Affymetrix 10 K 2.0 SNP array. Regions of high level amplification and homozygous deletion were identified and validated by quantitative PCR and FISH. Certain recurrent cytogenetic alterations were more frequent in recurrent/metastatic than in primary OS. These included deletion of 6q14.1, 6q16.2-q22.31, and 8p23.2-p12, amplification of 8q21.12, 8q22.3-q24.3 and 17p12, and loss of heterozygosity (LOH) at 2q24.3-q31.2, 5q11.2, 6p21.31-p21.1, 6q14.1-q16.2, 8p22-p12, 9q22.1, 10q21.1-q22.1, 10q23.31-q24.1, 12q15-q21.1 and 21q21.2-q21.3. Most of the LOH calls were associated with deletion, but a subset of them was associated with normal or increased copy number (CN). A consensus 3q13.31 deletion localized to a region within the limbic system-associated membrane protein (LSAMP) gene was also identified. The FISH evaluations demonstrated highly-localized homozygous or heterozygous LSAMP deletions in 6 of I I primary OS. qRT-PCR evaluations of the two major alternative LSAMP transcripts demonstrated reduced expression of 1b isoform transcript in each of three OS with LSAMP exon 1b deletion. Further, the I a isoform transcripts in these same OS had either reduced expression or a premature termination codon in LSAMP exon 2. This SNP genotyping study identified chromosomal aberrations associated with disease progression in OS and disclosed LSAMP as a novel tumor suppressor gene in OS. The study also demonstrated that CN and LOH analyses were able to detect distinct subsets of genetic abnormalities in OS.

引用

页码：775 / 788

页数：14

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