Harvey-ras allele deletion detected by in situ hybridization to Wilms' tumor chromosomes

Eccles, Michael R.; Millow, Lynn J.; Wilkins, Richard J.; Reeve, Anthony E.

doi:10.1007/bf00272999

Cited by 16 publications

(3 citation statements)

References 15 publications

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“…Chromosomal deletions of lip have been observed in neoplastic cells from some Wilms tumor patients (28,29). In most such tumors that were examined, c-rasH has been shown to be located outside the deleted segment (30,31); however, it was within the deleted segment in a few of them (32). The data are, thus, generally analogous to those that we have obtained, namely that c-src is outside of the region of the deletion.…”

Section: Discussionsupporting

confidence: 71%

c-src is consistently conserved in the chromosomal deletion (20q) observed in myeloid disorders.

Beau¹,

Westbrook²,

Dı́az³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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The proto-oncogene c-src has been mapped to two bands in human chromosomes, lp36 and 20q13, both of which are involved in rearrangements in human tumors. In particular, deletions (loss of part of a chromosome) of the long arm of chromosome 20, del(20q), are commonly observed in hematologic malignant diseases. By using in situ chromosomal hybridization of a c-src probe to metaphase cells prepared from leukemic bone marrow cells of three patients with a del(20q), we observed specific labeling on the deleted chromosome in each patient, indicating that the c-src locus was conserved. The presence on the rearranged chromosomes of c-src, which is normally located on the most distal band of 20q, indicated that the deletions were not terminal as they appeared to be on the basis of chromosome morphology, but rather that they were interstitial. The location of c-src relative to the distal breakpoint in these deletions is unknown. By using the v-src probe in Southern blot analysis of genomic DNA from three patients with a del(20q), we found that no major genomic rearrangements or amplification of the c-src genes had occurred within the regions homologous to v-src. Our observation that c-src is consistently preserved in these rearranged chromosomes suggests that this gene may play a role in the pathogenesis of some myeloid disorders.Nonrandom chromosomal rearrangements such as translocations and deletions are a prominent feature of human cancers, particularly of the leukemias and lymphomas (1, 2). During the past several years, a number of proto-oncogenes have been localized to chromosomal regions involved in these specific rearrangements (3,4). In at least two hematologic malignant diseases, the level of expression or the properties of a proto-oncogene product have been shown to be altered as a result of a chromosomal translocation [c-myc and the t(8;14) in Burkitt lymphoma (5, 6); c-abl and the t(9;22) in chronic myelogenous leukemia (7,8)]. Recently, we have focused our research efforts on identifying the chromosomal location of proto-oncogenes and their putative association with the nonrandom chromosomal rearrangements that occur in human malignant diseases. Investigations of one protooncogene, c-src, by somatic cell hybridization (9) and by in situ chromosomal hybridization (10) have demonstrated that the human genome contains two loci, at lp36 and 20q13, with strong homology to the coding region of this proto-oncogene. We now report the results of our expanded studies on the potential relationship of c-src to human malignant diseases characterized by abnormalities of the long arm (q) of chromosome 20.

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Section: Discussionsupporting

confidence: 71%

c-src is consistently conserved in the chromosomal deletion (20q) observed in myeloid disorders.

Beau¹,

Westbrook²,

Dı́az³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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“…According to this model, sporadic tumours develop following two independent events occurring in both copies of the same gene, while hereditary cases involve germline transmission of one altered gene and acquisition of a somatic mutation on the other allele. Although several studies in the 1980s reported WT1 ‐affected WTs behaving in similar manner to retinoblastoma [–], subsequently the ‘two‐hit’ model for WT has not been as strongly supported as it has been for retinoblastoma , perhaps due to genetic heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

Biallelic DICER1 mutations occur in Wilms tumours

Sabbaghian

et al. 2013

The Journal of Pathology

128

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DICER1 is an endoribonuclease central to the generation of microRNAs (miRNAs) and short interfering RNAs (siRNAs). Germline mutations in DICER1 have been associated with a pleiotropic tumour predisposition syndrome and Wilms tumour (WT) is a rare manifestation of this syndrome. Three WTs, each in a child with a deleterious germline DICER1 mutation, were screened for somatic DICER1 mutations and were found to bear specific mutations in either the RNase IIIa (n = 1) or the RNase IIIb domain (n = 2). In the two latter cases, we demonstrate that the germline and somatic DICER1 mutations were in trans, suggesting that the two-hit hypothesis of tumour formation applies for these examples of WT. Among 191 apparently sporadic WTs, we identified five different missense or deletion somatic DICER1 mutations (2.6%) in four individual WTs; one tumour had two very likely deleterious somatic mutations in trans in the RNase IIIb domain (c.5438A>G and c.5452G>A). In vitro studies of two somatic single-base substitutions (c.5429A>G and c.5438A>G) demonstrated exon 25 skipping from the transcript, a phenomenon not previously reported in DICER1. Further we show that DICER1 transcripts lacking exon 25 can be translated in vitro. This study has demonstrated that a subset of WTs exhibits two 'hits' in DICER1, suggesting that these mutations could be key events in the pathogenesis of these tumours.No conflicts of interest were declared. pleuropulmonary blastoma (PPB) syndrome (OMIM 601200) [7,8]. Several genes have been identified as being somatically mutated in WT, including WT1 , CTNNB1 , IGF2 , TP53 , WTX , DIS3L2 , FBXW7 and MYCN [5,9]. There are overlapping distributions of molecular abnormalities at 11p15, WTX , WT1 and CTNNB1 in WT [9,10], but other genes could be contributing to the aetiology of WT [3,[11][12][13]. WT histopathology is heterogeneous and tumours associated with different types of nephrogenic rests and histologies tend to show different underlying genetic changes [14,15]. A revised model for WT ontogeny takes into account genetic data (WT1 status, 11p15 imprint control region 1 methylation status, gene expression patterns of other genes) and histological data [14]. Nevertheless, each WT is thought to be of monoclonal origin [16].

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“…It is known that somatic changes, either rearrangements, point mutations, or deletions to the c-Ha-ras-1 oncogene, have been correlated to increased incidences of the tumour. This oncogene is localized at 1 lp14 immediately distal to the 1 lp13 segment and could be affected by a deletion in this area (Eccles et al, 1984). Other studies, however, have suggested that there must be another locus involved in the formation of Wilms tumour since no deletion of the oncogene was detected where AWTA was diagnosed (Huerre et al, 1983).…”

Section: Discussionmentioning

confidence: 97%

Prenatal diagnosis of del(11)(p13p15)

et al. 1988

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Prenatal diagnosis of del(11)(p13p15) was made on cultured amniotic fluid cells and confirmed on fetal skin fibroblasts after termination of pregnancy. Both irides appeared behind schedule in development by 2-3 weeks in reference to the gestational age of the fetus. It is suggested that the aniridia of the aniridia--Wilms tumour association is due to developmental arrest. Confirmation of this complex is difficult at mid-gestation without critical pathological study of the eyes.

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Harvey-ras allele deletion detected by in situ hybridization to Wilms' tumor chromosomes

Cited by 16 publications

References 15 publications

c-src is consistently conserved in the chromosomal deletion (20q) observed in myeloid disorders.

c-src is consistently conserved in the chromosomal deletion (20q) observed in myeloid disorders.

Biallelic DICER1 mutations occur in Wilms tumours

Prenatal diagnosis of del(11)(p13p15)

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