title: Identification of chromosomal aberrations associated with disease progression and a novel 3q13.31 deletion involving LSAMP gene in osteosarcoma.
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.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA. ccyen@vghtpe.gov.tw
authors.forename: Chueh-Chuan
authors.initials: CC
authors.lastname: Yen
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Chen
authors.forename: Tain-Hsiung
authors.initials: TH
authors.lastname: Chen
authors.forename: Winby York-Kwan
authors.initials: WY
authors.lastname: Chen
authors.forename: Paul Chih-Hsueh
authors.initials: PC
authors.lastname: Chen
authors.forename: Hong-Jen
authors.initials: HJ
authors.lastname: Chiou
authors.forename: Giun-Yi
authors.initials: GY
authors.lastname: Hung
authors.forename: Hung-Ta Hondar
authors.initials: HT
authors.lastname: Wu
authors.forename: Chao-Jung
authors.initials: CJ
authors.lastname: Wei
authors.forename: Cheng-Ying
authors.initials: CY
authors.lastname: Shiau
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Wu
authors.forename: Ta-Chung
authors.initials: TC
authors.lastname: Chao
authors.forename: Cheng-Hwai
authors.initials: CH
authors.lastname: Tzeng
authors.forename: Po-Min
authors.initials: PM
authors.lastname: Chen
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Yann-Jang
authors.initials: YJ
authors.lastname: Chen
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fletcher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D045744:Cell Line, Tumor; D002648:Child; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3; D018389:Codon, Nonsense; D005260:Female; D058851:GPI-Linked Proteins; D005784:Gene Amplification; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma / Q000235:genetics* / Q000556:secondary; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D018389:Codon, Nonsense; D058851:GPI-Linked Proteins; D012333:RNA, Messenger; C095362:limbic system-associated membrane protein