PMID- 21495021
OWN - NLM
STAT- MEDLINE
DCOM- 20111207
LR  - 20211020
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 117
IP  - 21
DP  - 2011 Nov 1
TI  - Genetic amplification of the vascular endothelial growth factor (VEGF) pathway 
      genes, including VEGFA, in human osteosarcoma.
PG  - 4925-38
LID - 10.1002/cncr.26116 [doi]
AB  - BACKGROUND: Osteosarcoma is the most common primary tumor of bone. It is a highly 
      vascular and extremely destructive malignancy that mainly affects children and 
      young adults. The authors conducted microarray-based comparative genomic 
      hybridization (aCGH) and pathway analyses to gain a systemic view of pathway 
      alterations in the genetically altered genes. METHODS: Recurrent amplified and 
      deleted genes that were detected by aCGH were subjected to an analysis based on 
      the Kyoto Encyclopedia of Genes and Genomes to identify the altered pathways. 
      Among the enriched pathways, vascular endothelial growth factor (VEGF) pathway 
      genes collectively were amplified, and alterations of this pathway were validated 
      by fluorescence in situ hybridization (FISH) and immunohistochemistry analyses in 
      58 formalin-fixed, paraffin-embedded osteosarcoma archival tissues that had 
      clinical follow-up information. RESULTS: The pathway enrichment analyses of the 
      aCGH data revealed that VEGF pathway genes, including the VEGFA gene itself, were 
      amplified significantly in osteosarcoma. Genetic amplification of the VEGFA gene, 
      both focally and in larger fragment, was validated by FISH analysis. It is 
      noteworthy that amplification of the VEGFA gene and elevated expression of the 
      VEGFA protein were associated significantly with microvascular density and 
      adverse tumor-free survival in patients with osteosarcoma. CONCLUSIONS: The 
      authors report for the first time that VEGF pathway genes, including the VEGFA 
      gene, are amplified in osteosarcoma. Amplification of the VEGFA gene is not only 
      an important mechanism for elevated VEGFA protein expression but also is a poor 
      prognostic factor for tumor-free survival. Combined classification of VEGFA gene 
      amplification and positive VEGFA protein expression may provide a more accurate 
      stratification method of selecting anti-VEGF therapy for patients with 
      osteosarcoma.
CI  - Copyright (c) 2011 American Cancer Society.
FAU - Yang, Jilong
AU  - Yang J
AD  - Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer 
      Hospital and Institute, Tianjin, China.
FAU - Yang, Da
AU  - Yang D
FAU - Sun, Yan
AU  - Sun Y
FAU - Sun, Baocun
AU  - Sun B
FAU - Wang, Guowen
AU  - Wang G
FAU - Trent, Jonathan C
AU  - Trent JC
FAU - Araujo, Dejka M
AU  - Araujo DM
FAU - Chen, Kexin
AU  - Chen K
FAU - Zhang, Wei
AU  - Zhang W
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - CA016672/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110414
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Bone Neoplasms/blood supply/*genetics
MH  - Disease-Free Survival
MH  - Gene Amplification
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Neovascularization, Pathologic
MH  - Osteosarcoma/blood supply/*genetics
MH  - Prognosis
MH  - Signal Transduction/genetics
MH  - Vascular Endothelial Growth Factor A/*genetics
PMC - PMC3465081
MID - NIHMS279688
EDAT- 2011/04/16 06:00
MHDA- 2011/12/13 00:00
PMCR- 2012/11/01
CRDT- 2011/04/16 06:00
PHST- 2010/12/11 00:00 [received]
PHST- 2011/02/02 00:00 [revised]
PHST- 2011/02/16 00:00 [accepted]
PHST- 2011/04/16 06:00 [entrez]
PHST- 2011/04/16 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2012/11/01 00:00 [pmc-release]
AID - 10.1002/cncr.26116 [doi]
PST - ppublish
SO  - Cancer. 2011 Nov 1;117(21):4925-38. doi: 10.1002/cncr.26116. Epub 2011 Apr 14.