Minimal residual disease in neuroblastoma: to GAGE or not to GAGE.
We assessed the utility of GAGE gene expression as a marker of minimal residual disease (MRD) in neuroblastoma. The GAGE gene family shows a high degree of homology (>90%), clustering into two subgroups. GAGE-1, -2, and -8 form one subset, almost identical among themselves, while GAGE-3 to -7 constitute the other subset. The entire GAGE family (GAGE-1-8) was studied by RT-PCR followed by Southern blotting to increase both the sensitivity and specificity of the technique. Surprisingly, expression of GAGE was detected in 59% of peripheral blood samples from normal controls (20/35) as well as in a similar proportion from neuroblastoma patients with localized disease (stages 1 and 2). The study of GAGE-1, -2, and -8 with specific primers lowered this percentage to 28% (10/35), of which only two (6%) showed a high level of expression (directly visualized after RT-PCR). We conclude that GAGE genes can show a variable, usually low level of illegitimate expression in normal blood cells, and therefore their use as MRD markers should be taken with caution.
Oltra
S
S
Unidad de Genética, Hospital Universitario La Fe, Valencia, Spain. jsoltra@uv.es
Martínez
F
F
Orellana
C
C
Grau
E
E
Fernández
J M
JM
Cañete
A
A
Castel
V
V
D000951:Antigens, Neoplasm; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D018365:Neoplasm, Residual / Q000097:blood / Q000235:genetics*; D009447:Neuroblastoma / Q000097:blood / Q000235:genetics*; D016415:Sequence Alignment
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C095365:GAGE1 protein, human; D009363:Neoplasm Proteins