Expression and sequence analysis of candidates for the 1p36.31 tumor suppressor gene deleted in neuroblastomas.
Neuroblastomas are characterized by 1p deletions, suggesting that a tumor suppressor gene (TSG) resides in this region. We have mapped the smallest region of deletion (SRD) to a 2 Mb region of 1p36.31 using microsatellite and single nucleotide polymorphisms. We have identified 23 genes in this region, and we have analysed these genes for mutations and RNA expression patterns to identify candidate TSGs. We sequenced the coding exons of these genes in 30 neuroblastoma cell lines. Although rare mutations were found in 10 of the 23 genes, none showed a pattern of genetic change consistent with homozygous inactivation. We examined the expression of these 23 genes in 20 neuroblastoma cell lines, and most showed readily detectable expression, and no correlation with 1p deletion. However, 7 genes showed uniformly low expression in the lines, and 2 genes (CHD5, RNF207) had virtually absent expression, consistent with the expected pattern for a TSG. Our mutation and expression analysis in neuroblastoma cell lines, combined with expression analysis in normal tissues, putative function and prior implication in neuroblastoma pathogenesis, suggests that the most promising TSG deleted from the 1p36 SRD is CHD5, but TNFRSF25, CAMTA1 and AJAP1 are also viable candidates.
Division of Oncology, The Children's Hospital of Philadelphia, Department of Pediatrics, The University of Pennsylvania, Philadelphia, PA 19104-4318, USA.
E R
ER
Okawa
T
T
Gotoh
J
J
Manne
J
J
Igarashi
T
T
Fujita
K A
KA
Silverman
H
H
Xhao
Y P
YP
Mosse
P S
PS
White
G M
GM
Brodeur
D045744:Cell Line, Tumor; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D020224:Expressed Sequence Tags; D017353:Gene Deletion; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D018895:Microsatellite Repeats; D009447:Neuroblastoma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA