Details

Autor(en) / Beteiligte

• Drake, Kylie M
• Ruteshouser, E Cristy
• Natrajan, Rachael
• Harbor, Phyllis
• Wegert, Jenny
• Gessler, Manfred
• Pritchard-Jones, Kathy
• Grundy, Paul
• Dome, Jeffrey
• Huff, Vicki
• Jones, Chris
• Aldred, Micheala A

Titel

Loss of Heterozygosity at 2q37 in Sporadic Wilms' Tumor: Putative Role for miR-562

Ist Teil von

• Clinical cancer research, 2009-10, Vol.15 (19), p.5985-5992

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Purpose: Wilms' tumor is a childhood cancer of the kidney with an incidence of ∼1 in 10,000. Cooccurrence of Wilms' tumor with 2q37 deletion syndrome, an uncommon constitutional chromosome abnormality, has been reported previously in three children. Given these are independently rare clinical entities, we hypothesized that 2q37 harbors a tumor suppressor gene important in Wilms' tumor pathogenesis. Experimental Design: To test this, we performed loss of heterozygosity analysis in a panel of 226 sporadic Wilms' tumor samples and mutation analysis of candidate genes. Results: Loss of heterozygosity was present in at least 4% of cases. Two tumors harbored homozygous deletions at 2q37.1, supporting the presence of a tumor suppressor gene that follows a classic two-hit model. However, no other evidence of second mutations was found, suggesting that heterozygous deletion alone may be sufficient to promote tumorigenesis in concert with other genomic abnormalities. We show that miR-562 , a microRNA within the candidate region, is expressed only in kidney and colon and regulates EYA1 , a critical gene for renal development. miR-562 expression is reduced in Wilms' tumor and may contribute to tumorigenesis by deregulating EYA1 . Two other candidate regions were localized at 2q37.3 and 2qter, but available data from patients with constitutional deletions suggest that these probably do not confer a high risk for Wilms' tumor. Conclusions: Our data support the presence of a tumor suppressor gene at 2q37.1 and suggest that, in individuals with constitutional 2q37 deletions, any increased risk for developing Wilms' tumor likely correlates with deletions encompassing 2q37.1. (Clin Cancer Res 2009;15(19):5985–92)