Abstract
Background: Mantle cell lymphoma (MCL) is derived from naïve CD5+ B-cells with the cytogenetic hallmark translocation 11;14. The presence of additional abnormalities is associated with blastoid variants in MCL (BMCL) and confers a poor prognosis. Many of these tumors also show deletion or loss of heterozygosity (LOH) of the ATM gene and biallelic ATM inactivation show significantly higher chromosomal imbalances. Case presentation: Here we report a 52 year-old male who presented to the clinic with worsening dyspnea, fever, chills, diffuse lymphadenopathy, splenomegaly and leukocytosis with blastoid cells circulating in blood. The bone marrow aspirate showed about 40% abnormal blast-looking cells and biopsy revealed a remarkable lymphoid infiltrate. The patient was diagnosed with blastoid variant mantle cell lymphoma (BMCL). Chromosome analysis on bone marrow showed a complex karyotype. FISH analysis from B-cell lymphoma panel showed bi-allelic amplification of ATM gene. Other abnormalities were present including CCND1/IGH fusion, confirming the MCL diagnosis, in addition to RB1 and p53 deletion. High resolution SNP-microarray studies showed complex copy number changes, especially on chromosomes 7 and 11, consistent with chromoanagenesis. Microarray studies also showed LOH at the ATM locus indicating the amplification seen on FISH is not biallelic. Conclusion: To the best of our knowledge, ATM gene amplification is not previously reported in BMCL and our case suggests a novel mechanism of ATM inactivation caused by chromoanagenesis resulting in mutant allele specific imbalance with copy number gain.
Original language | English (US) |
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Article number | 8 |
Journal | Molecular Cytogenetics |
Volume | 14 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2021 |
Keywords
- Blastoid mantle cell lymphoma (BMCL)
- Copy number gain (CNG)
- Fluorescence in situ hybridization (FISH)
- Loss of heterozygosity (LOH)
- Mantle cell lymphoma (MCL)
- Mutant allele specific imbalance (MASI)
- Single nucleotide polymorphism (SNP)
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Genetics
- Genetics(clinical)
- Biochemistry, medical