MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours
نویسندگان
چکیده
Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour.
منابع مشابه
DNA quantitation of Wilms' tumour (nephroblastoma) using flow cytometry and image analysis.
AIMS To compare flow cytometry (FCM) with image analysis (IA) in the DNA quantitation of Wilms' tumour (WT) and to correlate data so obtained with recognised clinical and pathological prognostic parameters. METHODS Thirty six patients with histologically proved WT diagnosed between 1980-89 were investigated. Fifteen patients had stage I disease, 10 stage II, six stage III, two stage IV and th...
متن کاملImprinting, expression, and localisation of DLK1 in Wilms tumours.
BACKGROUND Loss of imprinting (LOI) of the H19/IGF2 domain is a common feature of Wilms tumour. The GTL2/DLK1 domain is also imprinted and is structurally similar to H19/IGF2. The question arises as to whether DLK1 also undergoes LOI in Wilms tumour, or whether the LOI mechanism is restricted to the H19/IGF2 domain. AIM To investigate the imprinting status of DLK1 in Wilms tumours with IGF2 L...
متن کاملThe use of computer image analyses in the assessment of chosen histoclinical features of nephroblastoma cells in children.
The goal of the research was to assess the nuclear morphometric discriminant function (MV(f)) in the analyzed group of nephroblastomas and to evaluate its potential prognostic value. We found a statistically important correlation between favourable histology of Wilms' tumours (according to SIOP 93-01 and SIOP 2001 classifications of kidney tumours of childhood) and low values of MV(f) discrimin...
متن کاملCorrelation between a specific Wilms tumour suppressor gene (WT1) mutation and the histological findings in Wilms tumour (WT).
W ilms tumour (WT) is the most common malignant neoplasm of the kidney in childhood and accounts for approximately 8% of all childhood solid tumours. 2 Fetal rhabdomyomatous nephroblastoma (FRN) is a histological variant of WT characterised by a predominance of rhabdomyogenic components. Clinically, WT of the FRN type presents as a huge mass in younger patients and about 30% of them have bilate...
متن کاملSomatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumors
Wilms tumour is the most common childhood kidney cancer. Here we report the whole-exome sequencing of 44 Wilms tumours, identifying missense mutations in the microRNA (miRNA)-processing enzymes DROSHA and DICER1, and novel mutations in MYCN, SMARCA4 and ARID1A. Examination of tumour miRNA expression, in vitro processing assays and genomic editing in human cells demonstrates that DICER1 and DROS...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 6 شماره
صفحات -
تاریخ انتشار 2015