Patched 2, located in 1p32-34, is not mutated in high stage neuroblastoma tumors

Neuroblastoma is a childhood malignancy originating from cells of the sympa thetic nervous system, exhibiting a marked diversity in outcome, with spont aneous regression at one end of the spectrum and severe disease and death a t the other end. Features associated with frequent recurrence, a poor progn osis, 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 I, and has been mapped to 1p 32-34, a part of chromosome 1 frequently deleted in high stage neuroblastom a tumors. RT-PCR analysis of 9 neuroblastoma cell lines showed expression o f both Patched 1 and 2. We analyzed 14, mainly high stage, neuroblastoma tu mors for mutations in the Patched 2 gene with denaturing HPLC using the Wav e(TM) DNA fragment analysis system. In four tumor samples variations were d etected 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.