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Chromoanagenesis in Haematological Malignancy: Review of Samples from Patients with Acute Leukemia and MDS
Background: Complex chromosome rearrangements (CCRs) include a variety of structural aberrations grouped as chromothripsis, chromoanasynthesis and chromoplexy. Although the underlying mechanisms for these phenomena are unknown and likely to be different, they appear to originate from a single event....
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| Published in: | Blood 2023-11, Vol.142 (Supplement 1), p.1564-1564 |
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| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
| Online Access: | Get full text |
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| Summary: | Background:
Complex chromosome rearrangements (CCRs) include a variety of structural aberrations grouped as chromothripsis, chromoanasynthesis and chromoplexy. Although the underlying mechanisms for these phenomena are unknown and likely to be different, they appear to originate from a single event. While chromothripsis and chromoanasynthesis affect limited genome sites their role and genome associations in haematological malignancy remain to be elucidated.
Aims:
This study aimed to provide clarity on the location, incidence and association with TP53 gene profile of chromothripsis (cth) and chromoanasynthesis (cha) events in MDS/AML.
Methods:
We analysed data from routine investigations carried out by haematological malignancy diagnostic service (HMDS) at University College London Hospital (UCLH) on 2,506 samples of acute myeloid leukaemia (AML) and myelodysplasia (MDS), including G-banding, FISH (Cytocell), chromosome microarray analysis (CMA, Agilent) and target NGS(Illumina). Analysis of 87 samples with complex bone marrow karyotypes were reported following the ISCN 2020 as: (i) cth(alternating disomy and heterozygous loss along a chromosome or chromosomal segment) or (ii) cha (deletions and one or two copy number gains in a single chromosome or chromosome region including copy number variants without the clustered breakpoints of chromothripsis). Statistical analysis used RStudio (v 1.4.1106) to carry Pearson's chi-squared (χ²) and Fisher's exact (2-sided) tests.
Results:
Complex karyotypes harbouring cth and cha type aberrations were detected in 65 out of 727 AML and 22 out of 1779 MDS samples. The cth events were seen alongside cha in 67% of cases, rarely presenting as a sole abnormality (2%), while cha alone was found in 31% of samples. Most frequently cth was mapped at chromosome 21 (17%), chromosome 7 (15%), chromosome 17 and 19 (13%) and chromosome 5 (11%) (Fig.1a). In this cohort of 87cases, chromothripsis was found to be associated with TP53 deletions ( TP53Del/WT) in 7 (7%) and with TP53 mutations ( TP53Dpl/mut) in 22 (25%), while concurrent TP53 deletions and mutations ( TP53Del/mut) were detected in 29 (33%) ( p = 0.0005). Samples with TP53Del/mut harboured cth in chromosomes 7 (7%), 17 (6%), 8, 9, 19 and 21 (5%) whilst cases with TP53Dpl/mut had cth in chromosomes 21 (9%), 19 (8%), 5 (7%) and 7 (5%). (Fig 1 b).
The cha aberrations generally followed the genome location of cth events with some exception. Firstly, chromosomes X,13 and 21 appea |
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| ISSN: | 0006-4971 1528-0020 |
| DOI: | 10.1182/blood-2023-186105 |