Finally, microdissection of precursor structures combined with targeted genetic analysis may give insight into earliest genetic changes leading to progression of precursors from single cell to complex cluster; 3D reconstruction could also be applied to serially sectioned frozen tissue blocks of normal VHL kidney allowing for mass spectroscopic analysis for earliest proteomic change after microdissection, and applicability of proteomics for diagnosis of primary VHL tumors has been previously demonstrated [39]. Here, VHL is linked to von Hippel-Lindau disease.