This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baudry, D. Articles by Jeanpierre, C. Search for Related Content PubMed PubMed Citation Articles by Baudry, D. Articles by Jeanpierre, C.

WT1 Splicing Alterations in Wilms’ Tumors¹

INSERM U383 [D. B., M. H., M-O. C., C. Ju., C. Je.], Service d’Anatomie et de Cytologie Pathologique [J-C. F.], Clinique Chirurgicale Infantile [S. S.], Hôpital Necker-Enfants Malades, Université René Descartes, 75743 Paris Cedex 15, and Institut Gustave Roussy, 94805 Villejuif [M-F. T.], France

Hereditary and sporadic forms of tumors are generally related to germ-line and somatic mutations of the same tumor suppressor gene. Unexpectedly, in Wilms’ tumor, somatic mutations of the WT1 gene were found only occasionally in sporadic cases, although constitutional mutations of this gene are clearly associated with predisposition. It has been suggested that abnormal splicing may be another mode of somatic WT1 alteration. However, this idea was based on the analysis of a small series of tumors, precluding accurate evaluation of the frequency of such changes. To investigate WT1 changes at the somatic level in more detail, we analyzed the levels of the four isoform transcripts produced by alternative splicing events in a large series of 50 tumors, normal mature kidneys, and fetal kidneys. We characterized splicing alterations in 63% of sporadic Wilms’ tumors. Moreover, taking into account the decreased and increased overall levels of WT1 mRNA, the percentage of sporadic tumors with changes in WT1 expression reached 90%. Whether and how these alterations of expression play a role in the tumorigenic process remain to be evaluated.

This article has been cited by other articles:

				L. Xi, A. Feber, V. Gupta, M. Wu, A. D. Bergemann, R. J. Landreneau, V. R. Litle, A. Pennathur, J. D. Luketich, and T. E. Godfrey Whole genome exon arrays identify differential expression of alternatively spliced, cancer-related genes in lung cancer Nucleic Acids Res., November 1, 2008; 36(20): 6535 - 6547. [Abstract] [Full Text] [PDF]

				J. L. Chisa and D. T. Burke Mammalian mRNA Splice-Isoform Selection Is Tightly Controlled Genetics, March 1, 2007; 175(3): 1079 - 1087. [Abstract] [Full Text] [PDF]

				N. Kirschbaum-Slager, R. B. Parmigiani, A. A. Camargo, and S. J. de Souza Identification of human exons overexpressed in tumors through the use of genome and expressed sequence data Physiol Genomics, May 11, 2005; 21(3): 423 - 432. [Abstract] [Full Text] [PDF]

				C. Loirat, J. L. Andre, J. Champigneulle, C. Acquaviva, D. Chantereau, R. Bourquard, J. Elion, and E. Denamur WT1 splice site mutation in a 46,XX female with minimal-change nephrotic syndrome and Wilms' tumour Nephrol. Dial. Transplant., April 1, 2003; 18(4): 823 - 825. [Full Text] [PDF]