Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development
نویسندگان
چکیده
Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ∼25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer.
منابع مشابه
Breakage-fusion-bridge over and over again
*Correspondence to: Karel H.M. van Wely; Email: [email protected] The acquisition of massive but localized chromosome translocations, a phenomenon termed chromothripsis, has received widespread attention since its discovery over a year ago. Until recently, chromothripsis was believed to originate from a single catastrophic event, but the molecular mechanisms leading to this event are yet to ...
متن کاملChromothripsis and beyond: rapid genome evolution from complex chromosomal rearrangements.
Recent genome sequencing studies have identified several classes of complex genomic rearrangements that appear to be derived from a single catastrophic event. These discoveries identify ways that genomes can be altered in single large jumps rather than by many incremental steps. Here we compare and contrast these phenomena and examine the evidence that they arise "all at once." We consider the ...
متن کاملChromothripsis-like patterns are recurring, but heterogeneously distributed features in cancer: A survey of 22, 347 genomic copy number profiles
Chromothripsis is a newly discovered type of genomic rearrangement, characterized by locally clustered copy number aberrations. It has been proposed that it may arise during a single genome shattering event. It provides an alternative paradigm in cancer development, replacing the gradual accumulation of genomic changes with a one-off catastrophic event. However, the underlying mechanisms and it...
متن کاملIn Brief: Chromothripsis and cancer.
Chromothripsis is a one-step catastrophic event which plays an important role during cancer development. During chromothripsis, tens to hundreds of genomic rearrangements can occur within localized regions of the genome, and lead to the simultaneous creation of multiple cancer-driving aberrations. Given that chromothripsis has a cancer-wide incidence of 2-3%, its recent discovery has significan...
متن کاملChromothripsis and focal copy number alterations determine poor outcome in malignant melanoma.
Genetic changes during tumorigenesis are usually acquired sequentially. However, a recent study showed that in 2% to 3% of all cancers a single catastrophic event, termed chromothripsis, can lead to massive genomic rearrangements confined to one or a few chromosomes. To explore whether the degree of genomic instability and chromothripsis influences prognosis in cancer, we retrospectively applie...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 144 شماره
صفحات -
تاریخ انتشار 2011