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Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults [gene expression]

ABSTRACT: Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults [gene expression]

PROVIDER: PRJNA844310 | ENA |

REPOSITORIES: ENA

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Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults

Project description:Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults

| PRJNA844306 | ENA

Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults [SNP]

Project description:Chromothripsis is a mitotic catastrophe that arises from multiple double strand breaks and incorrect re-joining of one or a few chromosomes. We report on incidence, distribution, and features of chromothriptic events in T-cell acute lymphoblastic leukemias (T-ALL). Chromothripsis was detected in 11.6% of analyzed T-ALL and occurred only in adult cases with an immature phenotype (30%). It affected 1 to 4 chromosomes, and recurrently involved chromosomes 1, 6, 7, and 17. Abnormalities of genes typically associated with T-ALL were found at breakpoints of chromothripsis. In addition, it gave rise to new/rare alterations, such as, the SFPQ::ZFP36L2 fusion, reported in pediatric T-ALL, deletions of putative suppressors, such as IKZF2 and CSMD1, and amplification of the BCL2 gene. Compared to negative cases, chromothripsis positive T-ALL had a significantly higher level of MYCN expression, and a significant downregulation of RGCC, which is typically induced by TP53 in response to DNA damage. Furthermore we identified mutations and/or deletions of DNA repair/genome stability genes in all cases, and an association with NUP214 rearrangements in 33% of cases.

2022-08-17 | GSE205269 | GEO

Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults [SNP]

Project description:Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults [SNP]

| PRJNA844308 | ENA

Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults [RNA-seq]

Project description:Chromothripsis is a mitotic catastrophe that arises from multiple double strand breaks and incorrect re-joining of one or a few chromosomes. We report on incidence, distribution, and features of chromothriptic events in T-cell acute lymphoblastic leukemias (T-ALL). SNP array was performed in 103 T-ALL (39 ETP/near ETP, 59 non-ETP, and 5 with unknown stage of differentiation), including 38 children and 65 adults. Chromothripsis was detected in 11.6% of all T-ALL and occurred only in adult cases with an immature phenotype (12/39 cases; 30%). It affected 1 to 4 chromosomes, and recurrently involved chromosomes 1, 6, 7, and 17. Abnormalities of genes typically associated with T-ALL were found at breakpoints of chromothripsis. In addition, it gave rise to new/rare alterations, such as, the SFPQ::ZFP36L2 fusion, reported in pediatric T-ALL, deletions of putative suppressors, such as IKZF2 and CSMD1, and amplification of the BCL2 gene. Compared to negative cases, chromothripsis positive T-ALL had a significantly higher level of MYCN expression, and a significant downregulation of RGCC, which is typically induced by TP53 in response to DNA damage. Furthermore we identified mutations and/or deletions of DNA repair/genome stability genes in all cases, and an association with NUP214 rearrangements in 33% of cases.

2022-08-17 | GSE205266 | GEO

Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults [gene expression]

Project description:Chromothripsis is a mitotic catastrophe that arises from multiple double strand breaks and incorrect re-joining of one or a few chromosomes. We report on incidence, distribution, and features of chromothriptic events in T-cell acute lymphoblastic leukemias (T-ALL). SNP array was performed in 103 T-ALL (39 ETP/near ETP, 59 non-ETP, and 5 with unknown stage of differentiation), including 38 children and 65 adults. Chromothripsis was detected in 11.6% of all T-ALL and occurred only in adult cases with an immature phenotype (12/39 cases; 30%). It affected 1 to 4 chromosomes, and recurrently involved chromosomes 1, 6, 7, and 17. Abnormalities of genes typically associated with T-ALL were found at breakpoints of chromothripsis. In addition, it gave rise to new/rare alterations, such as, the SFPQ::ZFP36L2 fusion, reported in pediatric T-ALL, deletions of putative suppressors, such as IKZF2 and CSMD1, and amplification of the BCL2 gene. Compared to negative cases, chromothripsis positive T-ALL had a significantly higher level of MYCN expression, and a significant downregulation of RGCC, which is typically induced by TP53 in response to DNA damage. Furthermore we identified mutations and/or deletions of DNA repair/genome stability genes in all cases, and an association with NUP214 rearrangements in 33% of cases.

2022-08-17 | GSE205265 | GEO

Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults [RNA-seq]

Project description:Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults [RNA-seq]

| PRJNA844309 | ENA

Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-08-17 | GSE205270 | GEO

Chromothripsis drives DNA amplification in cancer cells developing drug resistance

Project description:Gene amplification leading to increased oncogene expression or anticancer drug resistance is a frequent event in cancer. Cytogenetic, genomic, and transcriptomic analyses were used to determine the initiating events of gene amplification in a tunable cell culture system developing resistance to chemotherapy. Chromosome shattering (chromothripsis) was found to be a major resistance driver through the production of extra-chromosomal double minutes either directly or subsequent to formation of a homogenous staining region (HSR). Formation and maintenance of double minutes were enhanced by PARP and DNA-PK activities. Double minutes were found to be highly dynamic, undergoing structural evolution to produce increased drug tolerance or re-integration into ectopic chromosomes under conditions of DNA damage. Genome rearrangement profiles produced through acquired drug resistance are similar to human cancer examples with oncogene amplification. Thus, chromothripsis is a driver of genome evolution that enables rapid acquisition of tolerance to altered growth conditions.

2020-09-14 | GSE119979 | GEO

Chromothripsis drives DNA amplification in cancer cells developing drug resistance

2020-09-23 | GSE119825 | GEO

Chromothripsis in AML

Project description:This dataset contains data from two acute myeloid leukaemia (AML) specimens processed with the Illumina CytoSNP-12 SNP array platform. SNP array data showed evidence of chromothripsis in these two specimens. Each deletion in the mosaic specimen was present in the same proportion of cells, which supports the view that the many breaks occur as a single event. Complementary FISH studies highlighted the inclusion of centromeres from different chromosomes during the formation of the new chromosomes.

2013-08-04 | GSE43522 | GEO

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