Figure 4.

A: Detection of VHL gene (3p25.5) LOH by PCR-SSCP analysis in tumor 1 (T₁; patient 1) and tumor 9 (T₂; patient 4) using a single nucleotide polymorphic marker (104/105) upstream of the coding region of the VHL gene. Arrowheads: Loss of the lower allele is detected in lane T₁ in patient 1, and loss of the upper allele is detected in lane T₂ in patient 4, containing DNA from pure populations of microdissected NET cells as compared with matched normal DNA (lanes N₁ and N₂, respectively) procured from the adjacent pancreas. B, C, and D: VHL gene deletion detected by FISH in interphase touch preparations of three VHL NETs. Green signal: α-Satellite centromeric marker specific for chromosome 3; red signal: chromosome 3p25 P1 probe containing the VHL gene. Both centromeric probes are retained in tumor cells and are seen in normal somatic cells (green signals appear as dots or as a “blush” when out of focus). B: Tumor 1 (patient 1) showing allelic deletion of the VHL gene in two tumor cells one red signal as compared with a normal somatic cell with two red signals (bottom). C: Allelic deletion of the VHL gene in NET cells (tumor 17, patient 7; one red signal. D: Allelic deletion of the VHL gene in NET cells (tumor 20, patient 10; one red signal).