PMID- 15298715
OWN - NLM
STAT- MEDLINE
DCOM- 20041110
LR  - 20220317
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 4
DP  - 2004 Aug 7
TI  - Genome-wide array comparative genomic hybridization analysis reveals distinct 
      amplifications in osteosarcoma.
PG  - 45
AB  - BACKGROUND: Osteosarcoma is a highly malignant bone neoplasm of children and 
      young adults. It is characterized by extremely complex karyotypes and high 
      frequency of chromosomal amplifications. Currently, only the histological 
      response (degree of necrosis) to therapy represent gold standard for predicting 
      the outcome in a patient with non-metastatic osteosarcoma at the time of 
      definitive surgery. Patients with lower degree of necrosis have a higher risk of 
      relapse and poor outcome even after chemotherapy and complete resection of the 
      primary tumor. Therefore, a better understanding of the underlying molecular 
      genetic events leading to tumor initiation and progression could result in the 
      identification of potential diagnostic and therapeutic targets. METHODS: We used 
      a genome-wide screening method - array based comparative genomic hybridization 
      (array-CGH) to identify DNA copy number changes in 48 patients with osteosarcoma. 
      We applied fluorescence in situ hybridization (FISH) to validate some of 
      amplified clones in this study. RESULTS: Clones showing gains (79%) were more 
      frequent than losses (66%). High-level amplifications and homozygous deletions 
      constitute 28.6% and 3.8% of tumor genome respectively. High-level amplifications 
      were present in 238 clones, of which about 37% of them showed recurrent 
      amplification. Most frequently amplified clones were mapped to 1p36.32 (PRDM16), 
      6p21.1 (CDC5L, HSPCB, NFKBIE), 8q24, 12q14.3 (IFNG), 16p13 (MGRN1), and 17p11.2 
      (PMP22 MYCD, SOX1,ELAC27). We validated some of the amplified clones by FISH from 
      6p12-p21, 8q23-q24, and 17p11.2 amplicons. Homozygous deletions were noted for 32 
      clones and only 7 clones showed in more than one case. These 7 clones were mapped 
      to 1q25.1 (4 cases), 3p14.1 (4 cases), 13q12.2 (2 cases), 4p15.1 (2 cases), 6q12 
      (2 cases), 6q12 (2 cases) and 6q16.3 (2 cases). CONCLUSIONS: This study clearly 
      demonstrates the utility of array CGH in defining high-resolution DNA copy number 
      changes and refining amplifications. The resolution of array CGH technology 
      combined with human genome database suggested the possible target genes present 
      in the gained or lost clones.
FAU - Man, Tsz-Kwong
AU  - Man TK
AD  - Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA. 
      tcman@txccc.org
FAU - Lu, Xin-Yan
AU  - Lu XY
FAU - Jaeweon, Kim
AU  - Jaeweon K
FAU - Perlaky, Laszlo
AU  - Perlaky L
FAU - Harris, Charles P
AU  - Harris CP
FAU - Shah, Shishir
AU  - Shah S
FAU - Ladanyi, Marc
AU  - Ladanyi M
FAU - Gorlick, Richard
AU  - Gorlick R
FAU - Lau, Ching C
AU  - Lau CC
FAU - Rao, Pulivarthi H
AU  - Rao PH
LA  - eng
GR  - U01 CA088126/CA/NCI NIH HHS/United States
GR  - CA88126/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Validation Study
DEP - 20040807
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Bone Neoplasms/*genetics
MH  - Child
MH  - Child, Preschool
MH  - *Chromosome Aberrations
MH  - Chromosome Deletion
MH  - *Chromosome Mapping
MH  - Chromosomes, Human, Pair 12
MH  - Chromosomes, Human, Pair 17
MH  - Chromosomes, Human, Pair 6
MH  - Chromosomes, Human, Pair 8
MH  - Clone Cells
MH  - Female
MH  - *Gene Amplification
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nucleic Acid Amplification Techniques/standards
MH  - Nucleic Acid Hybridization/*methods
MH  - Osteosarcoma/*genetics
PMC - PMC514550
EDAT- 2004/08/10 05:00
MHDA- 2004/11/13 09:00
PMCR- 2004/08/07
CRDT- 2004/08/10 05:00
PHST- 2004/05/04 00:00 [received]
PHST- 2004/08/07 00:00 [accepted]
PHST- 2004/08/10 05:00 [pubmed]
PHST- 2004/11/13 09:00 [medline]
PHST- 2004/08/10 05:00 [entrez]
PHST- 2004/08/07 00:00 [pmc-release]
AID - 1471-2407-4-45 [pii]
AID - 10.1186/1471-2407-4-45 [doi]
PST - epublish
SO  - BMC Cancer. 2004 Aug 7;4:45. doi: 10.1186/1471-2407-4-45.