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Functional inactivation of the WTX gene is not a frequent event in Wilms' tumors.

Abstract：

:For many years the precise genetic etiology of the majority of Wilms' tumors has remained unexplained. Recently, the WTX gene, mapped to chromosome Xq11.1, has been reported to be lost or mutated in approximately one-third of Wilms' tumors. Moreover, in female cases, the somatically inactivated alleles were found to invariantly derive from the active chromosome X. Consequently, WTX has been proposed as a 'one-hit' tumor suppressor gene. To provide further insights on the contribution of WTX to the development of the disease, we have examined 102 Wilms' tumors, obtained from 43 male and 57 female patients. Quantitative PCR analyses detected WTX deletions in 5 of 45 (11%) tumors from males, whereas loss of heterozygosity at WTX-linked microsatellites was observed in 9 tumors from 50 informative females (19%). However, in the latter group, using a combination of HUMARA assay and bisulfite-modified DNA sequencing, we found that the deletion affected the active chromosome X only in two cases (4%). Sequence analyses detected an inactivating somatic mutation of WTX in a single tumor, in which a strongly reduced expression of the mutant allele respect to the wild-type allele was observed, a finding not consistent with its localization on the active chromosome X. Overall, a functional somatic nullizygosity of the WTX gene was ascertained only in seven of the Wilms' tumors included in the study (approximately 7%). Our findings indicate that previously reported estimates on the proportion of Wilms' tumors due to WTX alterations should be reconsidered.

journal_name

Oncogene

journal_title

Oncogene

authors

Perotti D,Gamba B,Sardella M,Spreafico F,Terenziani M,Collini P,Pession A,Nantron M,Fossati-Bellani F,Radice P

doi

10.1038/onc.2008.93

subject

Has Abstract

pub_date

2008-07-31 00:00:00

pages

4625-32

issue

33

eissn

0950-9232

issn

1476-5594

pii

onc200893

journal_volume

27

pub_type

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