Chromothripsis

02/12/2015 - "Here, we report a case in which chromothripsis spontaneously cured a patient with WHIM syndrome, an autosomal dominant combined immunodeficiency disease caused by gain-of-function mutation of the chemokine receptor CXCR4. "

11/01/2014 - "In addition, alectinib was effective against EML4-ALK-positive tumors with ALK copy number gain mediated by chromothripsis."

01/01/2021 - "Thus, micronuclei are spatially restricted "mutation factories." Several large-scale DNA sequencing and bioinformatics studies over the last few years have revealed that most micronuclei display a mutational signature of chromothripsis immediately after their generation and the underlying molecular mechanisms have been dissected extensively. "
11/08/2023 - "Based on large-scale DNA sequencing of human tumours, the most frequent type of complex chromosome rearrangement is chromothripsis, a massive, localized and clustered rearrangement of one (or a few) chromosomes seemingly acquired in a single event. "
06/01/2023 - "Chromothripsis can be initiated by mis-segregation errors in mitosis3,4 or DNA metabolism5-7 that lead to entrapment of chromosomes within micronuclei and their subsequent fragmentation in the next interphase or following mitotic entry6,8-10. "
06/01/2023 - "Mitotic clustering facilitates the reassembly of acentric fragments into rearranged chromosomes lacking the extensive DNA copy-number losses that are characteristic of canonical chromothripsis. "
01/01/2022 - "Defects in DNA double-strand break repair, and in particular homologous recombination repair, have been linked with chromothripsis. "

01/01/2022 - "Here, we apply Hi-C to study chromatin organization before and after induction of chromothripsis in human cells. "
11/20/2023 - "Here, we discuss emerging mechanisms underlying chromothripsis from micronuclei and chromatin bridges, as well as highlight how this mutational cascade converges on the DNA damage response. "
01/01/2018 - "This chapter describes usage of different browsers to explore publicly available online data and to search for possible 3D chromatin changes involved during complex chromosomal rearrangements as chromothripsis. "
12/23/2016 - "Micronucleation of missegregated chromatin can lead to substantial chromosome rearrangements via chromothripsis. "
01/01/2016 - "Alternatively, chromothripsis can be caused by telomere crisis, a process that involves formation of dicentric chromosomes and chromatin bridges. "

10/01/1986 - "Induction of chromosome shattering by ultraviolet light and caffeine: the influence of different distributions of photolesions."
12/01/1981 - "Post-incubation with caffeine (1-2 mM) often resulted in chromosome shattering, which was a rare event in the absence of this compound. "
12/01/1981 - "Induction of chromosome shattering by ultraviolet irradiation and caffeine: comparison of whole-cell and partial-cell irradiation."
01/01/1980 - "Induction of chromosome shattering and micronuclei by ultraviolet light and caffeine. "
07/01/2009 - "In the present study, we used V79 Chinese hamster cells, stably transfected with histone H2BmRFP for live-cell observations, and induced generalized chromosome shattering (GCS) by the synergistic effect of UV irradiation and caffeine posttreatment. "

03/01/2014 - "Our study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis. "
01/01/2020 - "We present novel tools and workflows for the detection of different alteration types, including single-nucleotide variants (SNVs), small insertions and deletions (indels), copy-number variations (CNVs), loss of heterozygosity (LOH) and complex rearrangements, such as in chromothripsis. "
12/07/2020 - "Single nucleotide variations (SNV), short insertion or deletions (indels) and copy number alterations (CNA) were quantified using 5 quantitative metrics (SNV burden, indel burden, copy number alteration frequency-wGII, chromosomal arm event ratio-CAER, copy number amplitude) as well as 4 parameters that explored underlying oncogenic mechanisms (chromothripsis, double minutes, microsatellite instability and mutational signatures). "
11/07/2022 - "The results of our literature review show that the impact of such techniques in host genomes varies from small nucleotide polymorphisms to large genomic variation, such as segmental duplication, chromosome truncation, trisomy, chromothripsis, breakage fusion bridge, including large rearrangements of DNA vector-backbone sequences. "

10/01/2015 - "I then outline the challenges in translating newly discovered genome-wide or regional events, like trinucleotide mutation signatures, kataegis, and chromothripsis, into biomarkers, as well as the importance of incorporating prior biological knowledge. "
01/01/2022 - "Therefore, the aim of this study was to characterize the chromosomal aberration pattern in CUP depending on histological and clinical features and to assess its prognostic impact together with chromothripsis, tumor mutational burden (TMB), microsatellite instability (MSI), and mutational profiles as potential prognostic biomarkers. "
01/01/2023 - "Chromothripsis can thus be used as a potential indicator to help identify patients who will respond to ICB, which could complement established biomarkers."

01/01/2018 - "Recently, retrotransposons-a type of "jumping gene"-have been implicated as one means to generate double-stranded DNA breaks during chromothripsis and as sequences which can contribute to the final configuration of the derived chromosomes. "
01/01/2018 - "A Role for Retrotransposons in Chromothripsis."
01/01/2020 - "In this study, multiple DNA double-strand breaks (DSBs) were generated via the CRISPR/Cas9 system at centromere-specific retrotransposons in the human fungal pathogen Cryptococcus neoformans The resulting DSBs were repaired in a complex manner, leading to the formation of multiple interchromosomal rearrangements and new telomeres, similar to chromothripsis-like events. "

11/15/2020 - "In this study, an analysis of chromothripsis in 252 human breast cancers from two patient cohorts (149 metastatic breast cancers, 63 untreated primary tumors, 29 local relapses, and 11 longitudinal pairs) using whole-genome and whole-exome sequencing reveals that chromothripsis affects a substantial proportion of human breast cancers, with a prevalence over 60% in a cohort of metastatic cases and 25% in a cohort comprising predominantly luminal breast cancers. "
01/01/2020 - "ERα-related chromothripsis enhances concordant gene transcription on chromosome 17q11.1-q24.1 in luminal breast cancer."
01/01/2020 - "We found a group of luminal breast tumors displaying 17q-related chromothripsis for which antipsychotics can be repurposed as treatment adjuncts."

07/01/2009 - "In the present study, we used V79 Chinese hamster cells, stably transfected with histone H2BmRFP for live-cell observations, and induced generalized chromosome shattering (GCS) by the synergistic effect of UV irradiation and caffeine posttreatment. "

01/01/2023 - "We also describe the potential value of the CHP score in predicting the efficacy of immunotherapy and other treatments, elevating chromothripsis as a tool in clinical practice."
01/01/2023 - "Chromothripsis can be used as an independent predictor, and patients with low-CPSs experienced longer overall survival (OS) after immunotherapy [HR, 1.90; 95% confidence interval, 1.10-3.28; P = 0.019]. "
01/01/2023 - "In the immunotherapy cohort, copy number alteration-based chromothripsis scores (CPSs) were introduced to assess the extent of chromothripsis to evaluate its association with responsiveness to ICB. "
01/01/2023 - "Chromothripsis is correlated with reduced cytotoxic immune infiltration and diminished responsiveness to checkpoint blockade immunotherapy."

12/01/2012 - "Recent studies have identified a new phenomenon involving the simultaneous generation of tens to hundreds of genomic rearrangements, called chromothripsis. "
01/01/2019 - "Chromothripsis leads to fragmentation of chromosomes and their reconstitution with tens to hundreds of rearrangements clustered in small genome regions. "
01/01/2018 - "Chromothripsis is a mutational event driven by tens to hundreds of double-stranded DNA breaks which occur in a single event between a limited number of chromosomes. "
01/01/2015 - "The most striking example, chromothripsis, is characterized by tens or hundreds of rearrangements confined to a single chromosome or to local regions over a few chromosomes. "
09/01/2014 - "Of the 4 (57.1%) cases with complex karyotypes, 2 showed evidence of chromothripsis, a phenomenon in which tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. "

12/01/2019 - "Multiple chromosomal deletions (MIR1269, NRG3, ADK) in mCRC patients with chromothripsis are associated with better response to first line palliative FOLFOX-type chemotherapy and increased PFS."
01/01/2020 - "The complex karyotype formed after chemotherapy and radiotherapy, which is a criterion for an unfavorable prognosis of the disease, is considered as the equivalent of chromothripsis. "
12/01/2019 - "Materials and Methods: 10 mCRC patients with chromothripsis receiving 5-fluorouracil, oxaliplatin, leucovorin (FOLFOX) first-line palliative chemotherapy between August, 2011 and October, 2012 were selected for this study. "
11/01/2023 - "A dichotomy was revealed, in which neoplasms with evidence of chemotherapy-induced mutagenesis from platinum and melphalan were hypermutated and enriched for complex structural variants (ie, chromothripsis), whereas neoplasms with nonmutagenic chemotherapy exposures were genomically similar to de novo acute myeloid leukemia. "

01/01/2022 - "This review article will describe the new developments in the areas of biology with genomics and chromothripsis, and also focus on updates in treatment strategies in radiology, surgery, radiation, and medical oncology with cellular therapies. "
08/02/2012 - "Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy."
06/01/2023 - "We also discuss the mechanism of chromothripsis, chromothripsis in ACC tumorigenesis, and propose potential therapies targeting chromothripsis."
07/01/2018 - "Thus, we discuss potential implications of chromothripsis for cancer progression and therapy."
01/01/2014 - "Complex genomic rearrangements, such as chromothripsis, may affect cancer gene function and thereby have a major impact on cancer progression, prognosis, and therapy response."

12/01/2021 - "Carbon ion radiotherapy eradicates medulloblastomas with chromothripsis in an orthotopic Li-Fraumeni patient-derived mouse model."
12/01/2021 - "Potential role of carbon ion radiotherapy in chromothripsis-induced medulloblastoma and other malignancies."