Cytogenetic changes in Wilms tumorigenesis with emphasis on chromosome 22

[Truncated abstract] Overview: This thesis examines a cohort of 53 Wilms’ tumor from the same institution with morphology, associated nephrogenic rests, cytogenetics, SNP array studies, FISH and immunohistochemistry, particularly focusing on the involvement of chromosome 22 in Wilms tumor pathogenesis. Background: Wilms tumor is one of the commonest solid extra cranial malignant tumors of childhood. It is a tumor arising from the kidney, usually in young children (2 to 4 years old). Wilms tumor typically shows a characteristic triphasic histological pattern comprising blastemal, epithelial and stromal components reflecting its histologic recapitulation of nephrogenesis. Persistent clusters of renal embryonal cells, referred to as nephrogenic rests (NR) are presumed precursor lesions of Wilms tumors. There are two types of rest, perilobar (PLNR) and intralobar (ILNR), with each type of NR exhibiting a different malignant potential. Few PLNR progress to malignancy whereas malignant progression is frequent in ILNR. NR, in particular ILNR has shown LOH at 11p13 similar to that seen in the adjacent Wilms tumor, suggesting some clonal progression and functional inactivation of tumor suppression gene restricted to the 11p13 locus. PLNR has been associated with methylation changes at 11p15. It is considered that further genetic changes occur during the progression from a rest to a Wilms tumor. Chromosomal gains such as gains of chromosome 12, 18 and 1q are thought to be more common than losses in Wilms tumor.