Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location.

摘要: von Hippel Lindau disease (VHL) is an autosomal dominant familial cancer syndrome linked to alteration of the VHL tumor suppressor gene. Affected patients are predisposed develop pheochromocytomas and cystic solid tumors kidney, CNS, pancreas, retina, epididymis. However, organ involvement varies considerably among families has been shown correlate with underlying germline alteration. Clinically, we observed a paradoxically lower prevalence renal cell carcinoma (RCC) in complete deletion VHL. To determine if relationship existed between type disease, retrospectively evaluated 123 from 55 large deletions, including 42 intragenic partial deletions 13 by history radiographic imaging. Each individual family was scored for or pheochromocytoma. Germline were mapped using combination fluorescent situ hybridization (FISH) quantitative Southern blot analysis. An age-adjusted comparison demonstrated higher RCC relative (48.9 vs. 22.6%, p=0.007). This striking phenotypic dichotomy not seen lesions CNS (p=0.22), pancreas (p=0.72), pheochromocytoma (p=0.34). Deletion mapping revealed that development had even greater correlation retention HSPC300 (C3orf10), located within 30-kb region chromosome 3p, immediately telomeric (52.3 18.9%, p <0.001), suggesting presence neighboring gene genes critical maintenance RCC. Careful genotypic data objective measures will provide further insight into mechanisms formation.