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Chromothripsis in acute myeloid leukemia: Biological features and impact on survival
- Source :
- Leukemia, UnpayWall, ORCID, Microsoft Academic Graph, PubMed Central
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Chromothripsis is a one-step genome-shattering catastrophe resulting from disruption of one or few chromosomes in multiple fragments and consequent random rejoining and repair. This study defines incidence of chromothripsis in 395 newly diagnosed adult acute myeloid leukemia (AML) patients from three institutions, its impact on survival and its genomic background. SNP 6.0 or CytoscanHD Array (Affymetrix??) were performed on all samples. We detected chromothripsis with a custom algorithm in 26/395 patients. Patients harboring chromothripsis had higher age (p???=???0.002), ELN high risk (HR) (p?????0.001), lower white blood cell (WBC) count (p???=???0.040), TP53 loss, and/or mutations (p???<???0.001) while FLT3 (p???=???0.025), and NPM1 (p???=???0.032) mutations were mutually exclusive with chromothripsis. Chromothripsis-positive patients showed a worse overall survival (OS) (p???<???0.001) compared with HR patients (p???=???0.011) and a poor prognosis in a COX-HR optimal regression model. Chromothripsis presented the hallmarks of chromosome instability [i.e., TP53 alteration, 5q deletion, higher mean of copy number alteration (CNA), complex karyotype, alterations in DNA repair, and cell cycle] and focal deletions on chromosomes 4, 7, 12, 16, and 17. CBA. FISH showed that chromothripsis is associated with marker, derivative, and ring chromosomes. In conclusion, chromothripsis frequently occurs in AML (6.6%) and influences patient prognosis and disease biology.
- Subjects :
- 0301 basic medicine
Genome instability
Oncology
Adult
Male
medicine.medical_specialty
NPM1
Cancer Research
Adolescent
Ring chromosome
Polymorphism, Single Nucleotide
Article
03 medical and health sciences
Young Adult
Internal medicine
Chromosome instability
Antineoplastic Combined Chemotherapy Protocols
medicine
Biomarkers, Tumor
Humans
Genetic Predisposition to Disease
Ring Chromosomes
In Situ Hybridization, Fluorescence
Aged
Proportional Hazards Models
Aged, 80 and over
Chromothripsis
Hematology
business.industry
Myeloid leukemia
Adult Acute Myeloid Leukemia
Middle Aged
Prognosis
3. Good health
Chromosome Banding
Leukemia, Myeloid, Acute
030104 developmental biology
Treatment Outcome
Anesthesiology and Pain Medicine
Mutation
Female
business
Nucleophosmin
Subjects
Details
- ISSN :
- 14765551 and 08876924
- Database :
- OpenAIRE
- Journal :
- Leukemia
- Accession number :
- edsair.doi.dedup.....d4f40e80c8fa18f2be061a99e969ac9d