Mutational Inactivation of
            <i>STAG2</i>
            Causes Aneuploidy in Human Cancer

Solomon, David A.; Kim, Taeyeon; Díaz-Martínez, Laura A.; Fair, Joshlean; Elkahloun, Abdel G.; Harris, Brent T.; Toretsky, Jeffrey A.; Rosenberg, Steven A.; Shukla, Neerav; Ladanyi, Marc; Samuels, Yardena; James, C. David; Yu, Hongtao; Kim, Jung-Sik; Waldman, Todd

doi:10.1126/science.1203619

Cited by 398 publications

(452 citation statements)

References 24 publications

Supporting

Mentioning

423

Contrasting

Unclassified

Order By: Relevance

“…In contrast, in myeloid neoplasms, recurrent mutations and deletions have been detected in another study (Kon et al, 2013). Although there is dispute concerning the mutation of STAG2 in other carcinomas, it is reported by many scientists that there is a frequent mutation of STAG2 in bladder cancer (Solomon et al, 2011(Solomon et al, , 2013Balbás-Martínez et al, 2013). However, there is currently no evidence that shows whether loss of STAG2 leads to aneuploidy in bladder cells.…”

Section: Introductionmentioning

confidence: 93%

“…In addition, SA2 has direct contacts with specific regions of the C-terminal end of CTCF, and all other cohesin components are recruited through their interaction with SA2 (Xiao et al, 2011). In 2011, Waldman's group showed that targeted inactivation of STAG2 led to chromatid cohesion defects and aneuploidy (Solomon et al, 2011). Subsequently, the loss of expression of STAG2 has been reported in colorectal, gastric and prostate carcinomas; however there are few mutations in STAG2 in these carcinomas .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Loss of STAG2 causes aneuploidy in normal human bladder cells

Li¹,

Zhang²,

Tang³

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. The aim of this study was to determine how the function of human stromal antigen 2 (STAG2) plays an important role in proper chromosome separation. STAG2 mRNA in normal bladder cells and bladder tumor cells was evaluated by RT-PCR. The protein levels of STAG2 in normal bladder cells and bladder tumor cells were determined Loss of STAG2 function in cells by western blot. A cell proliferation assay was used to measure the growth of tumor cells and STAG2-inhibited normal cells, and STAG2-inhibited normal cells were subjected to karyotype analysis. Both STAG-2 mRNA and protein expression levels were lower in bladder cancer cells compared to the controls. Knockdown of STAG2 caused aneuploidy in normal bladder cells, leading to a decreased expression of the cohesin complex components SMC1, SMC3 and RAD21, but there was no obvious effect of STAG2 knockdown on cell proliferation. Our study indicated that abnormal expression of STAG2 could cause aneuploidy in normal bladder cells.

show abstract

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Loss of STAG2 causes aneuploidy in normal human bladder cells

Li¹,

Zhang²,

Tang³

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…Moreover, a genome-wide analysis of distribution of SA1 and SA2 revealed a unique role of cohesin-SA1 in gene regulation, such as at the c-myc and protocadherin loci (Remeseiro et al 2012b). It has also been reported that targeted inactivation of SA2 in a human cell line causes cohesion defects and aneuploidy (Solomon et al 2011). In the future, it will be of importance to determine how cohesin-SA1 and -SA2 are targeted to specific loci at a mechanistic level, although there is evidence that SA1 might use its AT-hook motif for telomere binding (Bisht et al 2013).…”

Section: Cohesin Establishes Sister Chromatid Cohesion During S Phasementioning

confidence: 99%

Chromosome Dynamics during Mitosis

Hirano

2015

Cold Spring Harb Perspect Biol

View full text Add to dashboard Cite

The primary goal of mitosis is to partition duplicated chromosomes into daughter cells. Eukaryotic chromosomes are equipped with two distinct classes of intrinsic machineries, cohesin and condensins, that ensure their faithful segregation during mitosis. Cohesin holds sister chromatids together immediately after their synthesis during S phase until the establishment of bipolar attachments to the mitotic spindle in metaphase. Condensins, on the other hand, attempt to "resolve" sister chromatids by counteracting cohesin. The products of the balancing acts of cohesin and condensins are metaphase chromosomes, in which two rod-shaped chromatids are connected primarily at the centromere. In anaphase, this connection is released by the action of separase that proteolytically cleaves the remaining population of cohesin. Recent studies uncover how this series of events might be mechanistically coupled with each other and intricately regulated by a number of regulatory factors.

show abstract

“…These genes include the RTK pathway genes (Met, Nf1, and Pdgfrb) as well as previously undescribed genes, such as Stag2, Traf3, Dmxl1, Foxj3, and Faf1, which are the top five glioma-specific candidate cancer genes listed in Dataset S3. Stag2, a gene encoding a subunit of cohesin, plays essential roles in genomic instability (47). Traf3 is an adaptor protein that directly binds to a number of TNF receptors.…”

Section: Discussionmentioning

confidence: 99%

Transposon mutagenesis identifies genes that transform neural stem cells into glioma-initiating cells

Koso

Takeda

Yew

et al. 2012

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

View full text Add to dashboard Cite

Neural stem cells (NSCs) are considered to be the cell of origin of glioblastoma multiforme (GBM). However, the genetic alterations that transform NSCs into glioma-initiating cells remain elusive. Using a unique transposon mutagenesis strategy that mutagenizes NSCs in culture, followed by additional rounds of mutagenesis to generate tumors in vivo, we have identified genes and signaling pathways that can transform NSCs into glioma-initiating cells. Mobilization of Sleeping Beauty transposons in NSCs induced the immortalization of astroglial-like cells, which were then able to generate tumors with characteristics of the mesenchymal subtype of GBM on transplantation, consistent with a potential astroglial origin for mesenchymal GBM. Sequence analysis of transposon insertion sites from tumors and immortalized cells identified more than 200 frequently mutated genes, including human GBM-associated genes, such as Met and Nf1, and made it possible to discriminate between genes that function during astroglial immortalization vs. later stages of tumor development. We also functionally validated five GBM candidate genes using a previously undescribed high-throughput method. Finally, we show that even clonally related tumors derived from the same immortalized line have acquired distinct combinations of genetic alterations during tumor development, suggesting that tumor formation in this model system involves competition among genetically variant cells, which is similar to the Darwinian evolutionary processes now thought to generate many human cancers. This mutagenesis strategy is faster and simpler than conventional transposon screens and can potentially be applied to any tissue stem/progenitor cells that can be grown and differentiated in vitro.

show abstract

Mutational Inactivation of STAG2 Causes Aneuploidy in Human Cancer

Cited by 398 publications

References 24 publications

Loss of STAG2 causes aneuploidy in normal human bladder cells

Loss of STAG2 causes aneuploidy in normal human bladder cells

Chromosome Dynamics during Mitosis

Transposon mutagenesis identifies genes that transform neural stem cells into glioma-initiating cells

Contact Info

Product

Resources

About