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Sister chromatid co...
Sister chromatid cohesion defects are associated with chromosomal copy number heterogeneity in high hyperdiploid childhood acute lymphoblastic leukemia
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- Moura-Castro, Larissa H. (författare)
- Lund University,Lunds universitet,Aneuploidi i cancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Aneuploidy in cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Peña-Martínez, Pablo (författare)
- Lund University,Lunds universitet,Målinriktade behandlingar för leukemi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Targeted therapies in leukemia,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Castor, Anders (författare)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Galeev, Roman (författare)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Larsson, Jonas (författare)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Järås, Marcus (författare)
- Lund University,Lunds universitet,Målinriktade behandlingar för leukemi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Targeted therapies in leukemia,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Yang, Minjun (författare)
- Lund University,Lunds universitet,Aneuploidi i cancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Aneuploidy in cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Paulsson, Kajsa (författare)
- Lund University,Lunds universitet,Aneuploidi i cancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Aneuploidy in cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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(creator_code:org_t)
- 2021-01-16
- 2021
- Engelska 8 s.
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Ingår i: Genes Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 60:6, s. 410-417
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Abstract
Ämnesord
Stäng
- High hyperdiploid acute lymphoblastic leukemia (ALL) is one of the most common malignancies in children. The main driver event of this disease is a nonrandom aneuploidy consisting of gains of whole chromosomes but without overt evidence of chromosomal instability (CIN). Here, we investigated the frequency and severity of defective sister chromatid cohesion—a phenomenon related to CIN—in primary pediatric ALL. We found that a large proportion (86%) of hyperdiploid cases displayed aberrant cohesion, frequently severe, to compare with 49% of ETV6/RUNX1-positive ALL, which mostly displayed mild defects. In hyperdiploid ALL, cohesion defects were associated with increased chromosomal copy number heterogeneity, which could indicate increased CIN. Furthermore, cohesion defects correlated with RAD21 and NCAPG mRNA expression, suggesting a link to reduced cohesin and condensin levels in hyperdiploid ALL. Knockdown of RAD21 in an ALL cell line led to sister chromatid cohesion defects, aberrant mitoses, and increased heterogeneity in chromosomal copy numbers, similar to what was seen in primary hyperdiploid ALL. In summary, our study shows that aberrant sister chromatid cohesion is frequent but heterogeneous in pediatric high hyperdiploid ALL, ranging from mild to very severe defects, and possibly due to low cohesin or condensin levels. Cases with high levels of aberrant chromosome cohesion displayed increased chromosomal copy number heterogeneity, possibly indicative of increased CIN. These abnormalities may play a role in the clonal evolution of hyperdiploid pediatric ALL.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- acute lymphoblastic leukemia
- aneuploidy
- chromosomal instability
- hyperdiploidy
- sister chromatid cohesion
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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