PMID- 18704985
OWN - NLM
STAT- MEDLINE
DCOM- 20081023
LR  - 20211020
IS  - 0008-543X (Print)
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 113
IP  - 6
DP  - 2008 Sep 15
TI  - Copy number gains in EGFR and copy number losses in PTEN are common events in 
      osteosarcoma tumors.
PG  - 1453-61
LID - 10.1002/cncr.23782 [doi]
AB  - BACKGROUND: Osteosarcoma cell lines and tumors have been shown to express 
      epidermal growth factor receptor (EGFR) and harbor amplifications at the EGFR 
      locus. In this study, the authors further analyzed the genomic features of EGFR 
      in osteosarcoma tumors and investigated whether they correlate with phosphatase 
      and tensin homolog (PTEN) expression and copy number status. METHODS: EGFR and 
      PTEN expression was assessed by immunohistochemistry (n = 28), and copy number 
      alterations at the EGFR and PTEN loci were surveyed using Affymetrix (Santa 
      Clara, Calif) 50K single nucleotide polymorphism (SNP) arrays (n = 31) and 
      fluorescence in situ hybridization (FISH) (n = 27). The EGFR tyrosine kinase 
      domain was sequenced to survey for activating mutations (n = 34). In addition, 
      EGFRvIII expression was assessed using reverse transcriptase polymerase chain 
      reaction (n = 24). Results were correlated with available clinical information on 
      59 patients, with a median age of 14.1 years (range, 5-23 years) and median 
      follow-up of 4.4 years. RESULTS: EGFR expression was detected in the majority of 
      osteosarcoma tumors surveyed (23 of 28; 82%). SNP arrays revealed evidence of 
      frequent copy number gains at 7p11.2 and losses at 10q23.21. A sizeable subset 
      (16 of 27 cases; 59%) showed gains at the EGFR locus using FISH (amplification in 
      4 of 27 [15%] and balanced chromosome 7 polysomy in 12 of 27 [44%]), and 12 cases 
      showed deletions at the PTEN locus (biallelic deletions in 4 of 27 [15%] and 
      monoallelic deletion in 9 of 27 [33%]). No activating mutations in the EGFR 
      tyrosine kinase domain, EGFRvIII expression, or association with clinical 
      findings were detected. CONCLUSIONS: EGFR expression and genomic gains at the 
      EGFR locus are prevalent in osteosarcoma tumors, which also commonly harbor 
      deletions at the PTEN locus.
CI  - (c) 2008 American Cancer Society.
FAU - Freeman, Serena S
AU  - Freeman SS
AD  - Department of Pathology, St. Jude Children's Research Hospital, Memphis, 
      Tennessee, USA.
FAU - Allen, Steven W
AU  - Allen SW
FAU - Ganti, Ramapriya
AU  - Ganti R
FAU - Wu, Jianrong
AU  - Wu J
FAU - Ma, Jing
AU  - Ma J
FAU - Su, Xiaoping
AU  - Su X
FAU - Neale, Geoff
AU  - Neale G
FAU - Dome, Jeffrey S
AU  - Dome JS
FAU - Daw, Najat C
AU  - Daw NC
FAU - Khoury, Joseph D
AU  - Khoury JD
LA  - eng
GR  - P01CA023099/CA/NCI NIH HHS/United States
GR  - R25 CA023944/CA/NCI NIH HHS/United States
GR  - P01 CA023099/CA/NCI NIH HHS/United States
GR  - U10 CA098543/CA/NCI NIH HHS/United States
GR  - R21CA98543/CA/NCI NIH HHS/United States
GR  - P30 CA021765/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Bone Neoplasms/*genetics/metabolism/pathology
MH  - Child
MH  - Child, Preschool
MH  - ErbB Receptors/*genetics/metabolism
MH  - Female
MH  - Gene Amplification
MH  - *Gene Dosage
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Mutation/genetics
MH  - Osteosarcoma/*genetics/metabolism/pathology
MH  - PTEN Phosphohydrolase/*genetics/metabolism
MH  - Polymorphism, Single Nucleotide
MH  - Prognosis
MH  - Survival Rate
PMC - PMC3529469
MID - NIHMS58342
COIS- Disclaimers: None of the authors have any significant potential conflicts of 
      interest to disclose. - This study was presented, in part, at the 2007 Annual 
      Meeting of the United States and Canadian Academy of Pathology.
EDAT- 2008/08/16 09:00
MHDA- 2008/10/24 09:00
PMCR- 2012/12/24
CRDT- 2008/08/16 09:00
PHST- 2008/08/16 09:00 [pubmed]
PHST- 2008/10/24 09:00 [medline]
PHST- 2008/08/16 09:00 [entrez]
PHST- 2012/12/24 00:00 [pmc-release]
AID - 10.1002/cncr.23782 [doi]
PST - ppublish
SO  - Cancer. 2008 Sep 15;113(6):1453-61. doi: 10.1002/cncr.23782.