Patched 2, located in 1p32-34, is not mutated in high stage neuroblastoma tumors.
Neuroblastoma is a childhood malignancy originating from cells of the sympathetic nervous system, exhibiting a marked diversity in outcome, with spontaneous regression at one end of the spectrum and severe disease and death at the other end. Features associated with frequent recurrence, a poor prognosis, and high tumor stage are loss of heterozygosity in the distal region of chromosome 1p and amplification of the N-myc gene. Patched 2 is a novel homologue to the tumor suppressor gene Patched 1, and has been mapped to 1p32-34, a part of chromosome 1 frequently deleted in high stage neuroblastoma tumors. RT-PCR analysis of 9 neuroblastoma cell lines showed expression of both Patched 1 and 2. We analyzed 14, mainly high stage, neuroblastoma tumors for mutations in the Patched 2 gene with denaturing HPLC using the Wave DNA fragment analysis system. In four tumor samples variations were detected within the coding sequence, and two of them gave rise to amino-acid substitutions. These variations were, however, also detected in normal DNA from the respective patients. We conclude that Patched 2 is expressed, but not frequently mutated, in high stage neuroblastomas and is therefore not likely to be involved in the genesis of this tumor.
Jögi
A
A
Department of Laboratory Medicine, Molecular Medicine, Lund University, University Hospital MAS, Malmö, Sweden.
Abel
F
F
Sjöberg
R M
RM
Toftgård
R
R
Zaphiropoulos
P G
PG
Påhlman
S
S
Martinsson
T
T
Axelson
H
H
D002851:Chromatography, High Pressure Liquid; D002878:Chromosomes, Human, Pair 1; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; D011956:Receptors, Cell Surface
D008565:Membrane Proteins; C000606236:PTCH1 protein, human; C000606238:PTCH2 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; D011956:Receptors, Cell Surface