Transcriptomes of aneuploid mouse T-ALL
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE57333 | GEO | 2014/07/01
SECONDARY ACCESSION(S): PRJNA246291
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptome analysis to map transcriptomes of Mps1DK p53null-driven aneuploid T-ALL, to determine correlation between copy number changes and expression changes and to map the transcriptional response to CIN Transcriptomes of T-ALL samples described in the accompanying manuscript were compared to the transcriptomes of thymocytes of 6-weeks old wild type mice
2014-07-01 | E-GEOD-57333 | biostudies-arrayexpress
Project description:Transcriptome analysis to map transcriptomes of Mad2 p53null-driven aneuploid liver cancers and T-ALLs, to determine correlation between copy number changes and expression changes and to map the transcriptional response to CIN Chromosome instability (CIN) leads to aneuploidy and copy number variations (CNVs). Even though both are hallmarks of cancer cells, aneuploidy inhibits proliferation of untransformed cells, suggesting that cancer cells have adapted to cope with CIN. The spindle assembly checkpoint (SAC) prevents CIN by monitoring chromosome attachment and sister chromatid tension in mitosis. By conditionally inactivating Mad2, an essential SAC gene, we find that SAC inactivation in T-cells or hepatocytes is remarkably well tolerated and becomes tumorigenic when placed in a p53null or p53+/- predisposed background. The resulting T-ALLs and HCCs are highly aneuploid, exhibit clonal copy number changes that are tumor specific despite ongoing CIN, indicating that CIN is a powerful driver of tumor evolution.
2017-03-20 | GSE63687 | GEO
Project description:Chromosome instability (CIN) leads to aneuploidy and copy number variations (CNVs). Even though both are hallmarks of cancer cells, aneuploidy inhibits proliferation of untransformed cells, suggesting that cancer cells have adapted to cope with CIN. The spindle assembly checkpoint (SAC) prevents CIN by monitoring chromosome attachment and sister chromatid tension in mitosis. By conditionally inactivating Mad2, an essential SAC gene, we find that SAC inactivation in T-cells or hepatocytes is remarkably well tolerated and becomes tumorigenic when placed in a p53null or p53+/- predisposed background. The resulting T-ALLs and HCCs are highly aneuploid, exhibit clonal copy number changes that are tumor specific despite ongoing CIN, indicating that CIN is a powerful driver of tumor evolution.
2017-03-20 | GSE63688 | GEO
Project description:Mad2 and p53 loss were combined in liver or T-cells specificely leading to early onset and highly aggressive aneuploid HCC and T-ALL. Tumours were characterized for (recurrrent) copy number changes with a focus on whole chromosome abnormalities. DNA content was compared to the DNA content of sex-matched uninfiltrated control liver samples from litter mates Chromosome instability (CIN) leads to aneuploidy and copy number variations (CNVs). Even though both are hallmarks of cancer cells, aneuploidy inhibits proliferation of untransformed cells, suggesting that cancer cells have adapted to cope with CIN. The spindle assembly checkpoint (SAC) prevents CIN by monitoring chromosome attachment and sister chromatid tension in mitosis. By conditionally inactivating Mad2, an essential SAC gene, we find that SAC inactivation in T-cells or hepatocytes is remarkably well tolerated and becomes tumorigenic when placed in a p53null or p53+/- predisposed background. The resulting T-ALLs and HCCs are highly aneuploid, exhibit clonal copy number changes that are tumor specific despite ongoing CIN, indicating that CIN is a powerful driver of tumor evolution.
2017-03-20 | GSE63686 | GEO
Project description:In Candida parapsilosis, transcriptomes of two aneuploid adaptors, TJ60 and TJ74, were compared to the euploid parent #12108. Cells were grown in YPD broth at 37C from OD600=0.1 to 1.0. Cells were collected and RNA was extracted.
2023-08-11 | E-MTAB-12322 | biostudies-arrayexpress
Project description:Chromosomal instability (CIN), defined as an increased occurrence of chromosome segregation errors during cell division, is a prominent form of genomic instability (Bakhoum and Avi Landau, 2017). It is the major cause of aneuploidy, an imbalanced complement of whole chromosomes or chromosome arms, which is the most prevalent genetic alteration in human cancers (Vasudevan et al., 2021; Santaguida and Amon, 2015). Importantly, aneuploidy is commonly associated with ongoing CIN through consecutive cell divisions (Shelzer et al. 2011; Passerini et al., 2016), resulting in intratumor genetic heterogeneity, a central driver of cancer evolution and therapeutic resistance (Sansregret et al., 2018; Ben-David and Amon, 2019). Indeed, aneuploidy has been shown to act both as a tumor suppressor and as a tumor initiator (Weaver et al., 2007; Silk et al., 2013; Vasudevan et al., 2020), most likely depending on the specific chromosomes that are gained or lost (Ben-David et al., 2011; Sack et al., 2018; Adell et al., 2023). Despite the ubiquitous presence of CIN in several aneuploid cancer types and its clinical relevance, its presence in B-cell acute lymphoblastic leukemia (B-ALL) remains largely unexplored owing to the impaired proliferation of leukemic cells in vitro and the lack of reliable experimental models to comprehensively assess chromosome segregation in vivo. B-ALL is the most frequent childhood cancer, with 75% of cases occurring in children under 6 years of age, and it is characterized by the accumulation of highly proliferative immature B-cell precursors in the bone marrow (BM) (Hunger and Mullighan, 2015). The presence of CIN and its contribution to aneuploid cB-ALL progression is largely unknown due to the lack of preclinical models to study actively dividing cells. Accordingly, studies of CIN in cB-ALL are limited to the characterization of chromosomal copy-number heterogeneity (chr-CNH) in primary cB-ALL samples, but there is controversy over its presence due to the different techniques used to assess karyotype variability (Raimondi et al., 1996; Talamo et al., 2010; Alpar et al., 2014; Heerema et al.; 2007; Ramos-Muntada et al., 2022). Here, we explored the presence and the levels of CIN in different clinically-relevant aneuploid subtypes of cB-ALL using single-cell whole-genome sequencing (WGS) of primary samples to reliably assess chr-CNH, and by generating a large cohort of PDX models from primary cB-ALL samples (cB-ALL-PDX). Our results in cB-ALL-PDX models revealed variable levels of CIN in aneuploid cB-ALL subtypes, which significantly correlate with intraclonal karyotype heterogeneity and with disease progression. Additionally, mass-spectrometry analyses of cB-ALL-PDX samples revealed a CIN “signature” enriched in mitosis and chromosome segregation regulatory pathways. We speculate that this signature identifies adaptive mechanisms to ongoing CIN in aneuploid cB-ALL cells, which displayed a transcriptional signature characterized by an impaired mitotic spindle as observed by RNA-sequencing (RNA-Seq) analyses of a large cohort of primary cB-ALL patient samples. Our work might help to improve stratification of patients with cB-ALL with different levels of CIN who could benefit in the future from new therapeutic approaches aiming to target ongoing CIN.
2023-09-15 | PXD042785 | Pride
Project description:Chromosome instability (CIN) leads to aneuploidy, a state in which cells have abnormal numbers of chromosomes affecting two out of three cancers. Continuous CIN in murine T-cells was previously shown to dramatically accelerate lymphomagenesis in a p53-deficient background. Despite the predicted ongoing CIN in our mouse model, we observed whole chromosome copy number changes that affected all lymphoma cells, suggesting that CIN is somehow suppressed in the aneuploid lymphomas or that selection for frequently lost/gained chromosomes outcompetes the CIN-imposed missegregation. To distinguish between these explanations and to examine karyotype dynamics in CIN lymphoma, we used a newly developed single-cell whole genome-sequencing (scWGS) platform that provides a complete and unbiased overview of copy number variations (CNV) in individual cells. In this study we applied single cell whole genome sequencing (scWGS) to map and quantify karyotype heterogeneity in primary mouse lymphoma and human leukaemia samples. We used cohorts of Mps1f/f; Lck-Cre+, Mps1f/f; p53f/f; Lck-Cre+ and Mps1f/f; p53f/+; Lck-Cre+ mice, and Lck-Cre- mice as controls. Mice were sacrificed when exhibiting signs of lymphoma (10-14 weeks of age, typically dyspnoea due to an enlarged thymus), thymuses were harvested, and primary T-ALL single cell suspensions were frozen for subsequent single cell sequencing analysis.
2016-04-16 | E-MTAB-4183 | biostudies-arrayexpress
Project description:DNA aneuploid sublines in sporadic colorectal cancers (CRCs) are quite frequent (about 85%) and likely the consequence of chromosomal instability and DNA copy number aberrations (CNAs). In order to gain insight into the mechanisms of the diploid-aneuploid transition in CRCs, we compared the CNA status in both diploid and aneuploid sublines. We used fresh/frozen material from 17 aneuploid CRCs, which was separated into 17 DNA diploid and 17 aneuploid sublines using enrichment of the epithelial component by multiparameter flow cytometry and sorting. CNA status of both sublines was obtained by array comparative genomic hybridization. The DNA diploid sublines from the aneuploid CRCs showed already CNAs, in particular, gains at 20p and 20q. The same aberrations were detected at increased frequencies in the corresponding DNA aneuploid sublines. Moreover, the very frequent gains/losses of chromosomes 4, 7, 8, 13, 15, and 18 in the DNA aneuploid sublines were absent or rare in the DNA diploid sublines from the same sporadic aneuploid CRCs. The comparison of the DNA diploid and aneuploid sublines from aneuploid CRCs suggests that 20p and 20q gains may play a role in the diploid-aneuploid transition. The 20q chromosomal arm appears of particular interest since it harbors several genes implicated in chromosomal instability.
2014-10-20 | GSE47148 | GEO
Project description:Cryptococcus neoformans lab strain H99 was used to obtain brefeldin A adaptors. Transcriptomes of 4 adaptors, each bearing a unique aneuploid, were compared to H99.
2022-09-29 | E-MTAB-12290 | biostudies-arrayexpress
Project description:Details of the series are available in the publication Cardoso J. et al., “Chromosomal instability in MYH- and APC-mutant adenomatous polyps”, Cancer Research, accepted for publication. Abstract of the publication: “The vast majority of colorectal cancers display genetic instability, either in the chromosomal (CIN) or microsatellite (MIN) forms. While CIN tumors are per definition aneuploid, MIN colorectal cancers, caused by loss of mismatch repair function, are usually near-diploid. Recently, bi-allelic germline mutations in the MYH gene, were found to be responsible for MAP (MYH associated polyposis), an autosomal recessive predisposition to multiple colorectal polyps, often indistinguishable from the dominant FAP (familial adenomatous polyposis) syndrome caused by inherited APC mutations. Here, we analyzed MYH- and APC-mutant polyps by combining laser-capture microdissection, isothermal genomic DNA amplification, and array-CGH (comparative genomic hybridization). Smoothed quantile regression methods were applied to the MAP and FAP genomic profiles to discriminate chromosomes predominantly affected by gains and losses. Up to 80% of the MAP polyps showed aneuploid changes, which is significantly higher than the 60% found among FAP polyps. Both MAP and FAP adenomas were characterized by frequent losses at chromosome 1p, 17, 19 and 22, and gains affecting chromosome 7 and 13. The observation that aneuploidy is already detectable at early stages of MYH-driven tumorigenesis raises the possibility that CIN may contribute significantly to accelerated tumor progression, increased cancer risk, and poor prognosis in MAP.” Keywords: repeat, BAC, CGH
2005-12-25 | GSE3898 | GEO