Publications Repository

Publications Repository

View item 
  •   Home
  • ICR Divisions
  • Breast Cancer Research
  • View item
  • Home
  • ICR Divisions
  • Breast Cancer Research
  • View item
JavaScript is disabled for your browser. Some features of this site may not work without it.

The NSD1 and EZH2 overgrowth genes, similarities and differences.

Thumbnail
View/Open
Accepted version (405.8Kb)
Date
2013-05
ICR Author
Rahman, Sabera
Author
Tatton-Brown, K
Rahman, N
Type
Journal Article
Metadata
Show full item record
Abstract
NSD1 and EZH2 are SET domain-containing histone methyltransferases that play key roles in the regulation of transcription through histone modification and chromatin modeling: NSD1 preferentially methylates lysine residue 36 of histone 3 (H3K36) and is primarily associated with active transcription, while EZH2 shows specificity for lysine residue 27 (H3K27) and is associated with transcriptional repression. Somatic dysregulation of NSD1 and EZH2 have been associated with tumorigenesis. NSD1, as a fusion transcript with NUP98, plays a key role in leukemogenesis, particularly childhood acute myeloid leukemia. EZH2 is a major proto-oncogene and mono- and biallelic activating and inactivating somatic mutations occur as early events in the development of tumors, particularly poor prognosis hematopoietic malignancies. Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap. NSD1 mutations that cause Sotos syndrome are loss-of-function, primarily truncating mutations or missense mutations at key residues in functional domains. EZH2 mutations that cause Weaver syndrome are primarily missense variants and the rare truncating mutations reported to date are in the last exon, suggesting that simple haploinsufficiency is unlikely to be generating the overgrowth phenotype although the exact mechanism has not yet been determined. Many additional questions about the molecular and clinical features of NSD1 and EZH2 remain unanswered. However, studies are underway to address these and, as more cases are ascertained and technology improves, it is hoped that these will, in time, be answered.
URI
https://repository.icr.ac.uk/handle/internal/1857
DOI
https://doi.org/10.1002/ajmg.c.31359
Collections
  • Breast Cancer Research
  • Genetics and Epidemiology
Subject
Humans
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
Growth
Germ-Line Mutation
Proto-Oncogenes
Polycomb Repressive Complex 2
Enhancer of Zeste Homolog 2 Protein
Histone Methyltransferases
Research team
Genetic Susceptibility
Language
eng
License start date
2013-05
Citation
American journal of medical genetics. Part C, Seminars in medical genetics, 2013, 163C (2), pp. 86 - 91

Browse

All of ICR repositoryICR DivisionsBy issue dateAuthorsTitlesPublication TypesThis collectionBy issue dateAuthorsTitlesPublication Types
  • Login
  • Registered office: The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP
    A Charity, Not for Profit. Company Limited by Guarantee.
    Registered in England No. 534147. VAT Registration No. GB 849 0581 02.