GLI activators are not required for ureteric cell function. The absence of HH signaling in the renal cortex of WT mice suggests that the cortex is a zone of low GLI activator and high GLI repressor levels. We determined the importance of exclusion of HH signaling activity from the cortical collecting ducts in mice with Ptc1-deficiency targeted to the UB lineage. Absence of ureteric cell Ptc1, a negative regulator of the HH signaling pathway, results in ectopic HH signaling activity in the cortical collecting ducts and ureteric bud tips. Ectopic HH signaling activity in the ureteric bud tips, which under normal circumstances is a domain of GLI repressor function, leads to decreased expression of Ret and Wnt11. These changes result in disruption of ureteric branching morphogenesis and nephrogenesis resulting in renal hypoplasia, likely due to impaired tip function. Remarkably, constitutive GLI3 repressor expression in the Ptc12/2UB background, restores ureteric tip cellspecific gene expression and normalizes renal morphogenesis, demonstrating a spatial requirement for GLI3 repressor in the Dexrazoxane hydrochloride proximal ureteric cells. Together, these results demonstrate a requirement for GLI3 repressor-dependent regulation of nephron number via ureteric tip cell Wnt11- and Ret-dependent functions. Recent genome-wide approaches, especially high resolution single nucleotide polymorphism arrays, enable evaluation of dynamic chromosomal as well as focal changes of CNG and loss of heterogeneity with very high resolution. Within a few years, these assays have identified several novel lesions with amplification and/or LOH across several organs. An important identification by SNP array was that uniparental disomy, which was originally described as a constitutional mechanism during meiosis, was frequently observed in several cancers. UPD arises when an individual inherits two copies of a particular chromosome from the 
same parent. The acquisition of UPD results in homozygosity for preexisting gene mutations with selective retention of the mutated allele. Including FLT3 and WT1 mutations in acute myeloid leukemia and JAK2 mutations in myeloproliferative disorders. To date, all reports of acquired UPD in solid tumors have been in association with the “two hit” inactivation of tumor suppressor genes. Our earlier observations regarding homozygous mutations and MASI led us to question the commonly held belief that tumorigenesis requires biallelic inactivation for tumor suppressor genes while the potent effects of dominant oncogenes preclude the necessity of loss of the wild type allele product. We examined a public database of mutations. We found, as expected, that most inactivating mutations of tumor suppressor genes were frequently accompanied by loss of the wild type allele. However, our earlier observations on homozygosity of oncogenes were confirmed by the finding that 20% of five activating oncogene mutations were homozygous in cell lines derived from multiple tumor types. As discussed below, the true incidence of MASI is considerably higher as quatitative copy number data are missing in the Sanger database. Thus MASI, while a long observed and expected phenomenon for tumor suppressor genes, is also present in an important subset of cells harboring mutant oncogenes. Other published evidence supports this concept. Detection of MASI of an oncogene requires three basic determinations: 1) detection of an oncogenic mutation; 2) copy number enumeration of the mutant gene in the tumor cells and 3) determination of the relative ratio of the mutant: wild type allele. Standard and widely accepted Ginsenoside-F5 methods for the first two determinations exist.