On the Complexity of Mechanisms and Consequences of Chromothripsis: An Update

Koltsova, Alla S.; Pendina, Anna A.; Efimova, Olga A.; Chiryaeva, Olga G.; Kuznetzova, T. V.; Baranov, V. S.

doi:10.3389/fgene.2019.00393

Cited by 59 publications

(62 citation statements)

References 137 publications

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“…The key-features, common to all chromothripsis events are the occurrence of numerous clustered chromosomal breakpoints, the low DNA copy number changes and the preservation of heterozygosity in the rearranged segments [14,15]. Several mechanisms involving telomere attrition, mitotic errors, abortive apoptosis, premature chromosome condensation, p53 defect, or viral integration were identified as cellular processes driving chromothripsis [16][17][18][19][20]. An attractive mechanistic explanation to link all these causal processes with the confined nature of genomic alterations generated by chromothripsis, is that the implicated chromosome(s) can be sequestrated into a micronucleus in which chromothripsis-related damages will occur [21,22].…”

Section: All-in-onementioning

confidence: 99%

Chromoanagenesis: a piece of the macroevolution scenario

Pellestor

Gatinois

2020

Mol Cytogenet

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Over the last decade, new types of massive and complex chromosomal rearrangements based on the chaotic shattering and restructuring of chromosomes have been identified in cancer cells as well as in patients with congenital diseases and healthy individuals. These unanticipated phenomena are named chromothripsis, chromoanasynthesis and chromoplexy, and are grouped under the term of chromoanagenesis. As mechanisms for rapid and profound genome modifications in germlines and early development, these processes can be regarded as credible pathways for genomic evolution and speciation process. Their discovery confirms the importance of genome-centric investigations to fully understand organismal evolution. Because they oppose the model of progressive acquisition of driver mutations or rearrangements, these phenomena conceptually give support to the concept of macroevolution, known through the models of "Hopeful Monsters" and the "Punctuated Equilibrium". In this review, we summarize mechanisms underlying chromoanagenesis processes and we show that numerous cases of chromosomal speciation and short-term adaptation could be correlated to chromoanagenesis-related mechanisms. In the frame of a modern and integrative analysis of eukaryote evolutionary processes, it seems important to consider the unexpected chromoanagenesis phenomena.

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Section: All-in-onementioning

confidence: 99%

Chromoanagenesis: a piece of the macroevolution scenario

Pellestor

Gatinois

2020

Mol Cytogenet

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“…The key difference between chromoanasynthesis and chromothripsis is that chromoanasynthesis harbors copy gains in addition to losses, whereas chromothripsis has almost complete absence of gains (14,38). Typically, chromoanasynthesis occurs in one or few chromosomes (12)(13)(14).…”

Section: Discussionmentioning

confidence: 99%

Multiple Chromoanasynthesis in a Rare Case of Sporadic Renal Leiomyosarcoma: A Case Report

et al. 2020

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We present the genetic profile of kidney giant leiomyosarcoma characterized by sequencing of 409 cancer related genes and chromosomal microarray analysis. Renal leiomyosarcomas are extremely rare neoplasms with aggressive behavior and poor survival prognosis. Most frequent somatic events in leiomyosarcomas are mutations in the TP53, RB1, ATRX, and PTEN genes, chromosomal instability (CIN) and chromoanagenesis. 67-year-old woman presented with a right kidney completely replaced by tumor. Immunohistochemical reaction on surgical material was positive to desmin and smooth muscle actin. Molecular genetic analysis revealed that tumor harbored monosomy of chromosomes 3 and 11, gain of Xp (ATRX) arm and three chromoanasynthesis regions (6q21-q27, 7p22.3-p12.1, and 12q13.11-q21.2), with MDM2 and CDK4 oncogenes copy number gains, whereas no copy number variations (CNVs) or tumor specific single nucleotide variants (SNVs) in TP53, RB1, and PTEN genes were present. We hypothesize that chromoanasynthesis in 12q13.11-q21.2 could be a trigger of observed CIN in this tumor.

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“…Notably, chromothripsis is mainly observed in chromosome arms, whereas centromeres were targeted in our studies 13 . However, some studies have indicated an association between chromothripsis break sites and the presence of transposon sequences 11, 60 . In our approach, the breaks were also located within transposon sequences, which are part of the centromeres.…”

Section: Discussionmentioning

confidence: 99%

Centromere scission drives chromosome shuffling and reproductive isolation

Yadav

Sun

Coelho

et al. 2019

Preprint

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AbstractA fundamental characteristic of eukaryotic organisms is the generation of genetic variation via sexual reproduction. Conversely, significant large-scale genome structure variations could hamper sexual reproduction, causing reproductive isolation and promote speciation. The underlying processes behind large-scale genome rearrangements are not well understood and include chromosome translocations involving centromeres. Recent genomic studies in the Cryptococcus species complex revealed that chromosome translocations generated via centromere recombination have reshaped the genomes of different species. 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 inter-chromosomal rearrangements and new telomeres, similar to chromothripsis-like events. The newly generated strains harboring chromosome translocations exhibited normal vegetative growth but failed to undergo successful sexual reproduction with the parental wild-type strain. One of these strains failed to produce any spores, while another produced ∼3% viable progeny. The germinated progeny exhibited aneuploidy for multiple chromosomes and showed improved fertility with both parents. All chromosome translocation events were accompanied without any detectable change in gene sequences and thus, suggest that chromosomal translocations alone may play an underappreciated role in the onset of reproductive isolation and speciation.

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On the Complexity of Mechanisms and Consequences of Chromothripsis: An Update

Cited by 59 publications

References 137 publications

Chromoanagenesis: a piece of the macroevolution scenario

Chromoanagenesis: a piece of the macroevolution scenario

Multiple Chromoanasynthesis in a Rare Case of Sporadic Renal Leiomyosarcoma: A Case Report

Centromere scission drives chromosome shuffling and reproductive isolation

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