Transcriptome-guided characterization of genomic rearrangements in a breast cancer cell line

Zhao, Qi; Caballero, Otávia L.; Lévy, Samuel; Stevenson, Brian J.; Iseli, Christian; Souza, Sandro J. de; Galante, Pedro A. F.; Busam, Dana; Leversha, Margaret; Chadalavada, Kalyani; Rogers, Yu-Hui; Venter, J. Craig; Simpson, Andrew J.G.; Strausberg, Robert L.

doi:10.1073/pnas.0812945106

Cited by 107 publications

(81 citation statements)

References 37 publications

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“…Because patients with NSD1 germ-line genetic disruption have an increased risk of developing malignancy before adulthood, including neuroblastoma, Wilms tumors, and hematological malignancies, a tumor-suppressor function for NSD1 might be proposed. This putative role is also supported by the presence of genomic rearrangements involving NSD1 in leukemias (10,15) and breast cancer cells (16). However, somatic mutations of NSD1 have not been described in sporadic neoplasms.…”

mentioning

confidence: 49%

Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma

Berdasco

Ropero

Setién

et al. 2009

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

189

139

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Sotos syndrome is an autosomal dominant condition characterized by overgrowth resulting in tall stature and macrocephaly, together with an increased risk of tumorigenesis. The disease is caused by loss-of-function mutations and deletions of the nuclear receptor SET domain containing protein-1 (NSD1) gene, which encodes a histone methyltransferase involved in chromatin regulation. However, despite its causal role in Sotos syndrome and the typical accelerated growth of these patients, little is known about the putative contribution of NSD1 to human sporadic malignancies. Here, we report that NSD1 function is abrogated in human neuroblastoma and glioma cells by transcriptional silencing associated with CpG island-promoter hypermethylation. We also demonstrate that the epigenetic inactivation of NSD1 in transformed cells leads to the specifically diminished methylation of the histone lysine residues H4-K20 and H3-K36. The described phenotype is also observed in Sotos syndrome patients with NSD1 genetic disruption. Expression microarray data from NSD1-depleted cells, followed by ChIP analysis, revealed that the oncogene MEIS1 is one of the main NSD1 targets in neuroblastoma. Furthermore, we show that the restoration of NSD1 expression induces tumor suppressorlike features, such as reduced colony formation density and inhibition of cellular growth. Screening a large collection of different tumor types revealed that NSD1 CpG island hypermethylation was a common event in neuroblastomas and gliomas. Most importantly, NSD1 hypermethylation was a predictor of poor outcome in high-risk neuroblastoma. These findings highlight the importance of NSD1 epigenetic inactivation in neuroblastoma and glioma that leads to a disrupted histone methylation landscape and might have a translational value as a prognostic marker.cancer ͉ DNA methylation ͉ epigenetics ͉ histone ͉ overgrowth

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mentioning

confidence: 49%

Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma

Berdasco

Ropero

Setién

et al. 2009

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

189

139

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“…RNA sequencing is highly accurate tool for measuring expression across the transcriptome and allows one to detect both known and novel features in a single assay; this enables the detection of transcript isoforms, gene fusions, single nucleotide variants, allele specific gene expression and other features without the prior knowledge [48,49]. mRNA sequencing is done to know about novel as well as known features of coding transcriptome.…”

Section: Expression Studies On Cancer With Transcriptome Sequencingmentioning

confidence: 99%

An overview on potential of in vitro studies and transcriptomics for cancer

Soni¹,

Gupta²,

Laeeq³

et al. 2017

Cancer Rep Rev

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The concept of cell lines emerged from the uncontrolled growth of cells called cancer; however cancer cell lines are not easy to develop. In current time a good number of human cancer and non cancer cell lines are available for research to find out a cure for this disease with the development of new therapies and medicines. According to different reports, cases of this disease are increasing day by day. Environmental pollution and different habits in modern life style viz. smoking, tobacco, etc. increasing the risk of cancer. Reports from several countries, including India on this issue are horrendous. The risk, severity and symptoms can be better understood by molecular level analysis of the disease. To date advancement of technology from microarray transcriptome analysis to transcriptome sequencing has been provided a deep insight into cancer. Sample size and ethical issues related to human necessitates the use of in vitro techniques alongwith such molecular techniques to get a thorough understanding of the disease and also provides a good prospectus.

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“…However, even the most imaginative approaches were of somewhat limited use because of the depth of sequencing and the information content of sequence tags. NextGen sequencing incorporating much deeper sequencing now provides glimpses of the rich information content that can be gleaned from the transcriptome, including not only alternative splice forms and non-protein encoding transcripts but also genomic alterations present in transcripts, such as somatic point mutations and gene alterations in fusions and truncations (Morin et al, 2008;Sugarbaker et al, 2008;Maher et al, 2009;Zhao et al, 2009).…”

Section: The Cancer Transcriptomementioning

confidence: 99%

Section: The Cancer Transcriptomementioning

confidence: 99%

“…In these studies Zhao et al, 2009), the transcriptomes of prostate and breast cancers were analysed for the presence of gene fusion events that result from chromosomal translocations. In the study by Zhao et al (2009), the pseudotetraploid breast cancer cell line HCC1954 was studied in comparison with a non-cancer-derived cell line from the same patient. Through mapping of B500 000 454-derived reads of RefSeq genes, eight novel gene fusion events were detected that reveal complex molecular events that result in fusion and truncated proteins, several in genes previously implicated in cancer.…”

Section: The Cancer Transcriptomementioning

confidence: 99%

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Whole-genome cancer analysis as an approach to deeper understanding of tumour biology

Strausberg

Simpson

2009

Br J Cancer

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Transcriptome-guided characterization of genomic rearrangements in a breast cancer cell line

Cited by 107 publications

References 37 publications

Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma

Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma

An overview on potential of in vitro studies and transcriptomics for cancer

Whole-genome cancer analysis as an approach to deeper understanding of tumour biology

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