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Stratification of Wilms tumor by genetic and epigenetic analysis

Content Provider	PubMed Central
Author	Scott, Richard H. Murray, Anne Baskcomb, Linda Turnbull, Clare Loveday, Chey Reem, Al-saadi Williams, Richard Breatnach, Fin Gerrard, Mary Hale, Juliet Kohler, Janice Pablo, Lapunzina Levitt, Gill A. Picton, Sue Pizer, Barry Ronghe, Milind D. Traunecker, Heidi Williams, Denise Kelsey, Anna Vujanic, Gordan M. Sebire, Neil J. Grundy, Paul Stiller, Charles A. Kathy, Pritchard-jones Douglas, Jenny Rahman, Nazneen
Copyright Year	2012
Abstract	Somatic defects at five loci, WT1, CTNNB1, WTX, TP53 and the imprinted 11p15 region, are implicated in Wilms tumor, the commonest childhood kidney cancer. In this study we analysed all five loci in 120 Wilms tumors. We identified epigenetic 11p15 abnormalities in 69% of tumors, 37% were H19 epimutations and 32% were paternal uniparental disomy (pUPD). We identified mutations of WTX in 32%, CTNNB1 in 15%, WT1 in 12% and TP53 in 5% of tumors. We identified several significant associations: between 11p15 and WTX (P=0.007), between WT1 and CTNNB1 (P<0.001), between WT1 and pUPD 11p15 (P=0.01), and a strong negative association between WT1 and H19 epimutation (P<0.001). We next used these data to stratify Wilms tumor into three molecular Groups, based on the status at 11p15 and WT1. Group 1 tumors (63%) were defined as 11p15-mutant and WT1-normal; a third also had WTX mutations. Group 2 tumors (13%) were WT1-mutant. They either had 11p15 pUPD or were 11p15-normal. Almost all had CTNNB1 mutations but none had H19 epimutation. Group 3 tumors (25%) were defined as 11p15-normal and WT1-normal and were typically normal at all five loci (P<0.001). We also identified a novel clinical association between H19 epimutation and bilateral disease (P<0.001). These data provide new insights into the pattern, order, interactions and clinical associations of molecular events in Wilms tumor.
Related Links	http://dx.doi.org/10.18632/oncotarget.468
Ending Page	335
Page Count	9
Starting Page	327
File Format	PDF
ISSN	19492553
e-ISSN	19492553
Journal	Oncotarget
Issue Number	3
Volume Number	3
Language	English
Publisher	Impact Journals LLC
Publisher Date	2012-03-01
Access Restriction	Open
Rights Holder	Impact Journals LLC
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Oncology

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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