Massive chromosomal rearrangement process linked to cancer
Chromothripsis: Single catastrophic event in a cell's history
Chromothripsis is a mutational process by which up to thousands of clustered chromosomal rearrangements occur in a single event in localised and confined genomic regions in one or a few chromosomes, and is known to be involved in both cancer and congenital diseases. It occurs through one massive genomic rearrangement during a single catastrophic event in the cell's history. It is believed that for the cell to be able to withstand such a destructive event, the occurrence of such an event must be the upper limit of what a cell can tolerate and survive.[1] The chromothripsis phenomenon opposes the conventional theory that cancer is the gradual acquisition of genomic rearrangements and somatic mutations over time.[2]
The simplest model as to how these rearrangements occur is through the simultaneous fragmentation of distinct chromosomal regions (breakpoints show a non-random distribution) and then subsequent imperfect reassembly by DNA repair pathways or aberrant DNA replication mechanisms. Chromothripsis occurs early in tumour development and leads to cellular transformation by loss of tumour suppressors and oncogene amplifications.[3] In 2015, it was found that chromothripsis can also be curative: a woman who had WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, an extremely rare autosomal dominant combined immunodeficiency disease, found her symptoms disappeared during her 30s after chromothripsis of chromosome 2 deleted the disease allele.[4]
The term chromothripsis is a neologism coined by scientists at the Wellcome Trust Sanger Institute[2] that comes from the Greek words χρῶμα, khrôma 'color' (representing chromosomes because they are strongly stained by particular dyes), and θρίψις, thrípsis 'shattering into pieces'.[2]
^Maher CA, Wilson RK (2012). "Chromothripsis and Human Disease: Piecing Together the Shattering Process". Cell. 148 (1–2): 29–32. doi:10.1016/j.cell.2012.01.006. PMC 3658123. PMID 22265399.
^ abcStephens PJ, Greenman CD, Fu B, et al. (2011). "Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development". Cell. 144 (1): 27–40. doi:10.1016/j.cell.2010.11.055. PMC 3065307. PMID 21215367.
^Forment JV, Kaidi A, Jackson SP (2012). "Chromothripsis and cancer: causes and consequences of chromosome shattering". Nature Reviews Cancer. 12 (10): 663–670. doi:10.1038/nrc3352. PMID 22972457. S2CID 28146930.
^David H. McDermott; Ji-Liang Gao; Qian Liu; Marie Siwicki; Craig Martens; Paejonette Jacobs; Daniel Velez; Erin Yim; Christine R. Bryke; Nancy Hsu; Zunyan Dai; Martha M. Marquesen; Elina Stregevsky; Nana Kwatemaa; Narda Theobald; Debra A. Long Priel; Stefania Pittaluga; Mark A. Raffeld; Katherine R. Calvo; Irina Maric; Ronan Desmond; Kevin L. Holmes; Douglas B. Kuhns; Karl Balabanian; Françoise Bachelerie; Stephen F. Porcella; Harry L. Malech; Philip M. Murphy (2015). "Chromothriptic Cure of WHIM Syndrome". Cell. 160 (4): 686–699. doi:10.1016/j.cell.2015.01.014. PMC 4329071. PMID 25662009.
disappeared during her 30s after chromothripsis of chromosome 2 deleted the disease allele. The term chromothripsis is a neologism coined by scientists...
evidence that chromothripsis may result in clinical benefit, in particular, the cure of a genetic disease. If a cell with chromothripsis dies, it is clinically...
chromothripsis, a phenomenon whereby a single catastrophic event causes “shattering” of a chromosome. The precise delineation between chromothripsis and...
ingests the concoction and transforms into a pigeon by undergoing "chromothripsis". Before Walter and Sterling can decide what to do next, Marcy and other...
neuroblastoma. They are a manifestation of gene amplification as a result of chromothripsis, during the development of tumors, which give the cells selective advantages...
genome instability by promoting a catastrophic mutational event called chromothripsis. Many micronucleus assays have been developed to test for the presence...
during replication. Compared to other cancer-related mutations, such as chromothripsis, kataegis is more commonly seen; it is not an accumulative process but...
et al. (November 2021). "Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma". Nature...
announced in 2011 is an extreme version of multiple mutations, called chromothripsis by its proponents. This idea, affecting only 2–3% of cases of cancer...
and has been described by a wide array of new terminology (including “chromothripsis,” “chromoplexy,” “chromoanagenesis,” “chromoanasynthesis,” “chromosome...
Molenaar JJ; et al. (2012). "Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes". Nature. 483 (7391): 589–593. Bibcode:2012Natur...
therapy. A woman with spontaneous remission of her WHIM syndrome due to chromothripsis in one of her blood stem cells has been identified. In support of these...
album's theme draws inspiration from the biological phenomenon known as chromothripsis, wherein living cells experience a catastrophic chain reaction resulting...
more of the following chromosomal events: incomplete trisomic rescue, chromothripsis-mediated partial trisomy rescue, U-type strand exchange, and/or rare...
patients with this Robertsonian translocation, leukaemia is initiated by chromothripsis; an event which breaks two chromosomes and reconfigures them in a flawed...
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