Bi-allelic amplification of ATM gene in blastoid variant of mantle cell lymphoma: a novel mechanism of inactivation due to chromoanagenesis?

Veronica Ortega, Christina Mendiola, Juana Rodriguez, William Ehman, You Wen Qian, Gopalrao Velagaleti

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Article number8
JournalMolecular Cytogenetics
Volume14
Issue number1
DOIs
StatePublished - 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

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