title: Significance of TP53 Mutation in Wilms Tumors with Diffuse Anaplasia: A Report from the Children's Oncology Group.
abstract: OBJECTIVE
  To investigate the role and significance of TP53 mutation in diffusely anaplastic Wilms tumors (DAWTs).
  
  
  METHODS
  All DAWTs registered on National Wilms Tumor Study-5 (n = 118) with available samples were analyzed for TP53 mutations and copy loss. Integrative genomic analysis was performed on 39 selected DAWTs.
  
  
  RESULTS
  Following analysis of a single random sample, 57 DAWTs (48%) demonstrated TP53 mutations, 13 (11%) copy loss without mutation, and 48 (41%) lacked both [defined as TP53-wild-type (wt)]. Patients with stage III/IV TP53-wt DAWTs (but not those with stage I/II disease) had significantly lower relapse and death rates than those with TP53 abnormalities. In-depth analysis of a subset of 39 DAWTs showed seven (18%) to be TP53-wt: These demonstrated gene expression evidence of an active p53 pathway. Retrospective pathology review of TP53-wt DAWT revealed no or very low volume of anaplasia in six of seven tumors. When samples from TP53-wt tumors known to contain anaplasia histologically were available, abnormal p53 protein accumulation was observed by immunohistochemistry.
  
  
  CONCLUSIONS
  These data support the key role of TP53 loss in the development of anaplasia in WT, and support its significant clinical impact in patients with residual anaplastic tumor following surgery. These data also suggest that most DAWTs will show evidence of TP53 mutation when samples selected for the presence of anaplasia are analyzed. This suggests that modifications of the current criteria to also consider volume of anaplasia and documentation of TP53 aberrations may better reflect the risk of relapse and death and enable optimization of therapeutic stratification. Clin Cancer Res; 22(22); 5582-91. ©2016 AACR.
authors.affiliation: Department of Pathology and Laboratory Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois.|Princess Maxima Centre for Pediatric Oncology, Utrecht, the Netherlands.|Department of Pathology, Pathan BV, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
authors.forename: Ariadne H A G
authors.initials: AH
authors.lastname: Ooms
authors.affiliation: Department of Pathology and Laboratory Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois.
authors.forename: Samantha
authors.initials: S
authors.lastname: Gadd
authors.affiliation: Office of Cancer Genomics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Gerhard
authors.affiliation: Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland.
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Smith
authors.affiliation: Office of Cancer Genomics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Guidry Auvil
authors.affiliation: Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, Maryland.
authors.forename: Daoud
authors.initials: D
authors.lastname: Meerzaman
authors.affiliation: Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, Maryland.
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Chen
authors.affiliation: Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, Maryland.
authors.forename: Chih Hao
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, Maryland.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yan
authors.affiliation: Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, Maryland.
authors.forename: Cu
authors.initials: C
authors.lastname: Nguyen
authors.affiliation: Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, Maryland.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, British Columbia, Canada.
authors.forename: Yussanne
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, British Columbia, Canada.
authors.forename: Zusheng
authors.initials: Z
authors.lastname: Zong
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, British Columbia, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mungall
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, British Columbia, Canada.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Moore
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, British Columbia, Canada.|Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Vicki
authors.initials: V
authors.lastname: Huff
authors.affiliation: Division of Pediatric Hematology/Oncology, Children's National Medical Center, Washington, DC.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Dome
authors.affiliation: Department of Biostatistics, University of Florida, Gainesville, Florida.
authors.forename: Yueh-Yun
authors.initials: YY
authors.lastname: Chi
authors.affiliation: Department of Biostatistics, University of Florida, Gainesville, Florida.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: Division of Pediatric Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: James I
authors.initials: JI
authors.lastname: Geller
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Mullighan
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: David A
authors.initials: DA
authors.lastname: Wheeler
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Hampton
authors.affiliation: Division of Hematology-Oncology and Transplantation, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University's Feinberg School of Medicine, Chicago, Illinois.|Northwestern Medicine Developmental Therapeutics Institute, Northwestern Memorial Hospital, Chicago, Illinois.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Walz
authors.affiliation: Princess Maxima Centre for Pediatric Oncology, Utrecht, the Netherlands.
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
authors.affiliation: Princess Maxima Centre for Pediatric Oncology, Utrecht, the Netherlands.|Department of Pathology, Reinier de Graaf Hospital, Delft, the Netherlands.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: de Krijger
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ross
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, Ohio.|Departments of Pathology and Pediatrics, Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Gastier-Foster
authors.affiliation: Department of Pathology and Laboratory Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois. Eperlman@luriechildrens.org.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Perlman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000708:Anaplasia / Q000235:genetics*; D002648:Child; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011884:Radius / Q000002:abnormalities*; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics*; D055815:Young Adult
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53