Date of Award
Doctor of Philosophy (PhD)
Gerard P. Zambetti, Ph.D.
Suzanne Baker, Ph.D. Edwards Park, Ph.D. Lawrence Pfeffer, Ph.D. D. Parker Suttle, Ph.D.
pediatric adrenocortical cancer, p53 mutations, gene expression
Pediatric adrenocortical cancer is extremely rare and often fatal (approximately 0.3-0.4 cases per million worldwide; 50% 5-year survival). The incidence of pediatric adrenocortical cancer in southern Brazil is 10-15 times higher than the worldwide incidence. Due to the rarity of adrenocortical cancer, especially in children, underlying gene dysregulation and mechanisms of tumorigenesis of the adrenal gland are very poorly described in the literature. However, it is well-known that the tumor suppressor p53, which is mutated in over 50% of all human cancers, is commonly mutated in pediatric adrenocortical cancer. In addition, evidence strongly suggests that if a child has adrenocortical cancer, it indicates a germline p53 mutation exists.
In order to provide an understanding of the etiology and the biology of this disease, blood and tumor samples from 35 pediatric adrenocortical tumor patients, including 24 from southern Brazil, were screened for p53 mutations. Matched blood and tumor samples were obtained as available. Of the 35 patient samples screened, 24 samples were entered into a novel gene expression study that exclusively investigated gene dysregulation in pediatric adrenocortical cancer; the first study of its kind. Overall findings from this study reveal the importance of screening for germline p53 mutations and provide fundamental insight into pediatric adrenocortical cancer.
West, Alina Nico , "Uncovering p53 Mutations and Abnormal Gene Expression in Pediatric Adrenocortical Cancer" (2007). Theses and Dissertations (ETD). Paper 293. http://dx.doi.org/10.21007/etd.cghs.2007.0347.