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Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Chromothripsis cth is a form of genomic instability leading to massive de novo structural chromosome rearrangements in a one-time catastrophic event.
It can cause cancer-promoting alterations, such as loss of sequences for tumor-suppressor genes, formation of oncogenic fusions, and oncogene amplifications. We investigated the genetic background and clinical significance of cth in childhood T-cell acute lymphoblastic leukemia T-ALL patients. For this purpose, whole-genome copy number alterations were analyzed in children with newly diagnosed T-ALL using high-density microarrays.
Cth was identified in 10 T-ALL samples 5. Chromothripsis is an infrequent genomic phenomenon in pediatric T-ALL but is significantly associated with cancer-predisposing syndromes and may associate with inferior prognosis. These immunological entities, as defined by differentiation arrest, are associated with recurrent molecular abnormalities, including sequence mutations, gene fusions, and structural aberrations. Although primary T-ALL is curable for most children given measurable residual disease MRD -based risk-adapted intensive chemotherapy, salvage treatment for relapsed T-ALL is usually far less effective.
In contrast to the excellently defined prognostic significance of the majority of molecular subtypes of childhood B-cell precursor ALL, relatively few genetic lesions with proven clinical relevance exist in pediatric T-ALL. An extreme form of a complex karyotype is chromothripsis cth , which is caused by genome instability and leads to massive DNA breakage and repair in cancer cells in a single catastrophic event. In cth, tens to hundreds of genomic rearrangements are acquired in a few cell divisions and remain clustered within the focal chromosomal region [ 7 ].
