✍ Scribed by Clericuzio, Carol L. ;D'Angio, Giulio J. ;Duncan, Marilyn ;Green, Daniel M. ;Knudson, Alfred G.
No coin nor oath required. For personal study only.
The Workshop addressed under three rubrics the progress made and future directions in research conceming primary renal tumors of childhood.
Current information implicates involvement of four distinct loci in the development of Wilms tumor. One locus is at chromosome I I p 13, the second and third are at chromosomes 1 lp15 and 16q, and the fourth is at an as yet unidentified locus. The presence of a fourth locus is suggested by exclusion of linkage to 1 lp13, llp15, and 16q markers in familial Wilms tumor. Three groups have recently independently identified WT1, the Wilms tumor suppressor gene at chromosome 1 lp13. Subsequently, several studies have produced data supporting the role of WTl as a Wilms tumor gene, but several interesting questions remain to be answered. These include: "What is the role of the WTl germ line mutations in the development of Wilms tumor?" "Does the two-hit model demonstrated to be applicable for the development of retinoblastoma apply to Wilms tumor insofar as 1 1 p 13 is concerned?" "Is WT1 implicated in the non-hereditary cases?' Much current research is directed toward answering these and similar questions regarding the function of WTl in normal and pathologic genitourinary development, and specifically its function in Wilms tumorigenesis. Meanwhile, identification of WT2, the putative Wilms tumor locus at chromosome 1 1~1.5, is a major focus of work at several laboratories, work that is made difficult by the fact that the region of interest harbors several genes. Clarification is required as to whether the gene is directly linked to or separate from the gene for the Beckwith-Wiedemann syndrome; whether it is, in fact, a tumor gene; or whether it acts indirectly through alterations of cell kinetics leading to overgrowths of various tissues, such as muscle and the adrenal cortex. Coordinated research to address these questions might speed their answers.
Loss of tumor heterozygosity for markers at chromosome 16q can be demonstrated in approximately one fifth of all Wilms tumor cases analyzed. This evidence strongly suggests a gene at this locus that is also involved in Wilms tumor, and its role as a possible tumor progression gene, rather than tumor initiation gene, is currently under study.
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Our objechves include: i) determirung correlations between Wilms' tumor-specific molecular genehc events and clinicopathologc features; (ii) identifyrig hrther DNA/chromosomal aberrations; and (iii) establishing a Wilms' tumor tissue bank. To this end, a Witms' tumor biology protocol has been develo