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309169 occurrences (No.70 in the rank) during 5 years in the PubMed. [cache]
354) We propose that chromothripsis is a primary mechanism that accelerates genomic DNA rearrangement and amplification into ecDNA and enables rapid acquisition of tolerance to altered growth conditions.
* Chromothripsis drives the evolution of gene amplification in cancer.
- Focal chromosomal amplification contributes to the initiation of cancer by mediating overexpression of oncogenes1-3, and to the development of cancer therapy resistance by increasing the expression of genes whose action diminishes the efficacy of anti-cancer drugs. Here we used whole-genome sequencing of clonal cell isolates that developed chemotherapeutic resistance to show that chromothripsis is a major driver of circular extrachromosomal DNA (ecDNA) amplification (also known as double minutes) through mechanisms that depend on poly(ADP-ribose) polymerases (PARP) and the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). Longitudinal analyses revealed that a further increase in drug tolerance is achieved by structural evolution of ecDNAs through additional rounds of chromothripsis. In situ Hi-C sequencing showed that ecDNAs preferentially tether near chromosome ends, where they re-integrate when DNA damage is present. Intrachromosomal amplifications that formed initially under low-level drug selection underwent continuing breakage-fusion-bridge cycles, generating amplicons more than 100 megabases in length that became trapped within interphase bridges and then shattered, thereby producing micronuclei whose encapsulated ecDNAs are substrates for chromothripsis. We identified similar genome rearrangement profiles linked to localized gene amplification in human cancers with acquired drug resistance or oncogene amplifications. We propose that chromothripsis is a primary mechanism that accelerates genomic DNA rearrangement and amplification into ecDNA and enables rapid acquisition of tolerance to altered growth conditions.
=>茂み, 成長, 増加, 発展, 栽培, 腫よう, 成長物
Overview of noun growth
The noun growth has 7 senses (first 5 from tagged texts)
1. (37) growth, growing, maturation, development, ontogeny, ontogenesis -- ((biology) the process of
an individual organism growing organically; a purely biological unfolding of events involved in an
organism changing gradually from a simple to a more complex level; "he proposed an indicator of
osseous development in children")
2. (20) growth -- (a progression from simpler to more complex forms; "the growth of culture")
3. (3) increase, increment, growth -- (a process of becoming larger or longer or more numerous or
more important; "the increase in unemployment"; "the growth of population")
4. (3) growth -- (vegetation that has grown; "a growth of trees"; "the only growth was some salt
grass")
5. (1) emergence, outgrowth, growth -- (the gradual beginning or coming forth; "figurines presage
the emergence of sculpture in Greece")
6. growth -- ((pathology) an abnormal proliferation of tissue (as in a tumor))
7. growth -- (something grown or growing; "a growth of hair")
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