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

Chueh Chuan Yen, Wei Ming Chen, Tain Hsiung Chen, Winby York Kwan Chen, Paul Chih Hsueh Chen, Hong Jen Chiou, Giun Yi Hung, Hung Ta Hondar Wu, Chao Jung Wei, Cheng Ying Shiau, Yu Chung Wu, Ta Chung Chao, Cheng Hwai Tzeng, Po Min Chen, Chi Hung Lin, Yann Jang Chen, Jonathan A. Fletcher

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

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 11 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 1a 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.

Original languageEnglish
Pages (from-to)775-788
Number of pages14
JournalInternational journal of oncology
Volume35
Issue number4
DOIs
StatePublished - Oct 2009

Keywords

  • Limbic system-associated membrane protein
  • Oligonucleotide arrays
  • Osteosarcoma
  • Real-time quantitative PCR
  • Single-nucleotide polymorphism
  • Tumor suppressor gene

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