Copy number gains in EGFR and copy number losses in PTEN are common events in osteosarcoma tumors.
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.
Freeman
Serena S
SS
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Allen
Steven W
SW
Ganti
Ramapriya
R
Wu
Jianrong
J
Ma
Jing
J
Su
Xiaoping
X
Neale
Geoff
G
Dome
Jeffrey S
JS
Daw
Najat C
NC
Khoury
Joseph D
JD
D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009154:Mutation / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D015996:Survival Rate
C512478:EGFR protein, human; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human