TRIM28 variants and Wilms' tumour predisposition

TRIM28 was recently identified as a Wilms' tumour (WT) predisposition gene, with germline pathogenic variants identified in around 1% of isolated and 8% of familial WT cases. TRIM28 variants are associated with epithelial WT, but the presence of other tumour components or anaplasia does not exc...

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Published inThe Journal of pathology Vol. 254; no. 4; pp. 494 - 504
Main Authors Hol, Janna A, Diets, Illja J, Krijger, Ronald R, Heuvel‐Eibrink, Marry M, Jongmans, Marjolijn CJ, Kuiper, Roland P
Format Journal Article
LanguageEnglish
Published Chichester, UK John Wiley & Sons, Ltd 01.07.2021
Wiley Subscription Services, Inc
Subjects
cancer predisposition
Children
Embryogenesis
embryonic kidney development
Genes, Wilms Tumor
Genetic Predisposition to Disease - genetics
Genetic screening
Heredity
Humans
Immunohistochemistry
Invited Review
Invited Reviews
KAP1
Kidney Neoplasms - genetics
Mutation
nephroblastoma
TIF1beta
Transcription factors
TRIM28
Tripartite Motif-Containing Protein 28 - genetics
Tumor suppressor genes
Tumorigenesis
Tumors
Wilms Tumor - genetics
Wilms' tumour
nephroblastoma
KAP1
TRIM28
Wilms' tumour
cancer predisposition
embryonic kidney development
TIF1beta
Online AccessGet full text
ISSN0022-3417
1096-9896
1096-9896
DOI10.1002/path.5639

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Abstract TRIM28 was recently identified as a Wilms' tumour (WT) predisposition gene, with germline pathogenic variants identified in around 1% of isolated and 8% of familial WT cases. TRIM28 variants are associated with epithelial WT, but the presence of other tumour components or anaplasia does not exclude the presence of a germline or somatic TRIM28 variant. In children with WT, TRIM28 acts as a classical tumour suppressor gene, with both alleles generally disrupted in the tumour. Therefore, loss of TRIM28 (KAP1/TIF1beta) protein expression in tumour tissue by immunohistochemistry is an effective strategy to identify patients carrying pathogenic TRIM28 variants. TRIM28 is a ubiquitously expressed corepressor that binds transcription factors in a context‐, species‐, and cell‐type‐specific manner to control the expression of genes and transposable elements during embryogenesis and cellular differentiation. In this review, we describe the inheritance patterns, histopathological and clinical features of TRIM28‐associated WT, as well as potential underlying mechanisms of tumourigenesis during embryonic kidney development. Recognizing germline TRIM28 variants in patients with WT can enable counselling, genetic testing, and potential early detection of WT in other children in the family. A further exploration of TRIM28‐associated WT will help to unravel the diverse and complex mechanisms underlying WT development. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
AbstractList TRIM28 was recently identified as a Wilms' tumour (WT) predisposition gene, with germline pathogenic variants identified in around 1% of isolated and 8% of familial WT cases. TRIM28 variants are associated with epithelial WT, but the presence of other tumour components or anaplasia does not exclude the presence of a germline or somatic TRIM28 variant. In children with WT, TRIM28 acts as a classical tumour suppressor gene, with both alleles generally disrupted in the tumour. Therefore, loss of TRIM28 (KAP1/TIF1beta) protein expression in tumour tissue by immunohistochemistry is an effective strategy to identify patients carrying pathogenic TRIM28 variants. TRIM28 is a ubiquitously expressed corepressor that binds transcription factors in a context‐, species‐, and cell‐type‐specific manner to control the expression of genes and transposable elements during embryogenesis and cellular differentiation. In this review, we describe the inheritance patterns, histopathological and clinical features of TRIM28‐ associated WT, as well as potential underlying mechanisms of tumourigenesis during embryonic kidney development. Recognizing germline TRIM28 variants in patients with WT can enable counselling, genetic testing, and potential early detection of WT in other children in the family. A further exploration of TRIM28‐ associated WT will help to unravel the diverse and complex mechanisms underlying WT development. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
TRIM28 was recently identified as a Wilms' tumour (WT) predisposition gene, with germline pathogenic variants identified in around 1% of isolated and 8% of familial WT cases. TRIM28 variants are associated with epithelial WT, but the presence of other tumour components or anaplasia does not exclude the presence of a germline or somatic TRIM28 variant. In children with WT, TRIM28 acts as a classical tumour suppressor gene, with both alleles generally disrupted in the tumour. Therefore, loss of TRIM28 (KAP1/TIF1beta) protein expression in tumour tissue by immunohistochemistry is an effective strategy to identify patients carrying pathogenic TRIM28 variants. TRIM28 is a ubiquitously expressed corepressor that binds transcription factors in a context‐, species‐, and cell‐type‐specific manner to control the expression of genes and transposable elements during embryogenesis and cellular differentiation. In this review, we describe the inheritance patterns, histopathological and clinical features of TRIM28‐associated WT, as well as potential underlying mechanisms of tumourigenesis during embryonic kidney development. Recognizing germline TRIM28 variants in patients with WT can enable counselling, genetic testing, and potential early detection of WT in other children in the family. A further exploration of TRIM28‐associated WT will help to unravel the diverse and complex mechanisms underlying WT development. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
TRIM28 was recently identified as a Wilms' tumour (WT) predisposition gene, with germline pathogenic variants identified in around 1% of isolated and 8% of familial WT cases. TRIM28 variants are associated with epithelial WT, but the presence of other tumour components or anaplasia does not exclude the presence of a germline or somatic TRIM28 variant. In children with WT, TRIM28 acts as a classical tumour suppressor gene, with both alleles generally disrupted in the tumour. Therefore, loss of TRIM28 (KAP1/TIF1beta) protein expression in tumour tissue by immunohistochemistry is an effective strategy to identify patients carrying pathogenic TRIM28 variants. TRIM28 is a ubiquitously expressed corepressor that binds transcription factors in a context-, species-, and cell-type-specific manner to control the expression of genes and transposable elements during embryogenesis and cellular differentiation. In this review, we describe the inheritance patterns, histopathological and clinical features of TRIM28-associated WT, as well as potential underlying mechanisms of tumourigenesis during embryonic kidney development. Recognizing germline TRIM28 variants in patients with WT can enable counselling, genetic testing, and potential early detection of WT in other children in the family. A further exploration of TRIM28-associated WT will help to unravel the diverse and complex mechanisms underlying WT development. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.TRIM28 was recently identified as a Wilms' tumour (WT) predisposition gene, with germline pathogenic variants identified in around 1% of isolated and 8% of familial WT cases. TRIM28 variants are associated with epithelial WT, but the presence of other tumour components or anaplasia does not exclude the presence of a germline or somatic TRIM28 variant. In children with WT, TRIM28 acts as a classical tumour suppressor gene, with both alleles generally disrupted in the tumour. Therefore, loss of TRIM28 (KAP1/TIF1beta) protein expression in tumour tissue by immunohistochemistry is an effective strategy to identify patients carrying pathogenic TRIM28 variants. TRIM28 is a ubiquitously expressed corepressor that binds transcription factors in a context-, species-, and cell-type-specific manner to control the expression of genes and transposable elements during embryogenesis and cellular differentiation. In this review, we describe the inheritance patterns, histopathological and clinical features of TRIM28-associated WT, as well as potential underlying mechanisms of tumourigenesis during embryonic kidney development. Recognizing germline TRIM28 variants in patients with WT can enable counselling, genetic testing, and potential early detection of WT in other children in the family. A further exploration of TRIM28-associated WT will help to unravel the diverse and complex mechanisms underlying WT development. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Author Krijger, Ronald R
Heuvel‐Eibrink, Marry M
Kuiper, Roland P
Hol, Janna A
Diets, Illja J
Jongmans, Marjolijn CJ
AuthorAffiliation 1 Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
3 Department of Pathology University Medical Center Utrecht Utrecht The Netherlands
4 Department of Genetics University Medical Center Utrecht/Wilhelmina Children's Hospital Utrecht The Netherlands
2 Department of Human Genetics Radboud University Medical Center Nijmegen The Netherlands
AuthorAffiliation_xml – name: 2 Department of Human Genetics Radboud University Medical Center Nijmegen The Netherlands
– name: 1 Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
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Keywords nephroblastoma
KAP1
TRIM28
Wilms' tumour
cancer predisposition
embryonic kidney development
TIF1beta
Language English
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Snippet TRIM28 was recently identified as a Wilms' tumour (WT) predisposition gene, with germline pathogenic variants identified in around 1% of isolated and 8% of...
TRIM28 was recently identified as a Wilms' tumour (WT) predisposition gene, with germline pathogenic variants identified in around 1% of isolated and 8% of...
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pubmed
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wiley
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SubjectTerms cancer predisposition
Children
Embryogenesis
embryonic kidney development
Genes, Wilms Tumor
Genetic Predisposition to Disease - genetics
Genetic screening
Heredity
Humans
Immunohistochemistry
Invited Review
Invited Reviews
KAP1
Kidney Neoplasms - genetics
Mutation
nephroblastoma
TIF1beta
Transcription factors
TRIM28
Tripartite Motif-Containing Protein 28 - genetics
Tumor suppressor genes
Tumorigenesis
Tumors
Wilms Tumor - genetics
Wilms' tumour
Title TRIM28 variants and Wilms' tumour predisposition
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fpath.5639
https://www.ncbi.nlm.nih.gov/pubmed/33565090
https://www.proquest.com/docview/2537525371
https://www.proquest.com/docview/2488170050
https://pubmed.ncbi.nlm.nih.gov/PMC8252630
Volume 254
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