A novel t(X;21)(p11.4;q22.12) translocation adds to the role of BCOR and RUNX1 in myelodysplastic syndromes and acute myeloid leukemias

• Published in: Genes chromosomes & cancer Vol. 63; no. 4; pp. e23235 - n/a
• Main Authors: Mavridou, Elena, Lema Fernandez, Anair Graciela, Nardelli, Carlotta, Pierini, Valentina, Quintini, Martina, Arniani, Silvia, Di Giacomo, Danika, Crescenzi, Barbara, Matteucci, Caterina, Sambani, Constantina, Mecucci, Cristina
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.04.2024; Wiley Subscription Services, Inc
• Subjects: Acute myeloid leukemia; Adult; Aged; BCOR; Chromosome translocations; Chromosomes, Human, Pair 21 - genetics; Core Binding Factor Alpha 2 Subunit - genetics; deletions; Female; Fusion protein; Gene fusion; Genes; Haploinsufficiency; Humans; Karyotypes; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - pathology; Male; Middle Aged; Mutation; Myelodysplastic syndrome; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - pathology; myeloid malignancies; Proto-Oncogene Proteins - genetics; Regulatory sequences; Repressor Proteins - genetics; RUNX1; Runx1 protein; t(X;21); Transcriptomes; Translocation, Genetic; myeloid malignancies; BCOR; t(X;21); deletions; RUNX1
• ISSN: 1045-2257; 1098-2264; 1098-2264
• DOI: 10.1002/gcc.23235

In myeloid neoplasms, both fusion genes and gene mutations are well‐established events identifying clinicopathological entities. In this study, we present a thus far undescribed t(X;21)(p11.4;q22.12) in five cases with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The translocation was isolated or accompanied by additional changes. It did not generate any fusion gene or gene deregulation by aberrant juxtaposition with regulatory sequences. Molecular analysis by targeted next‐generation sequencing showed that the translocation was accompanied by at least one somatic mutation in TET2, EZH2, RUNX1, ASXL1, SRSF2, ZRSR2, DNMT3A, and NRAS genes. Co‐occurrence of deletion of RUNX1 in 21q22 and of BCOR in Xp11 was associated with t(X;21). BCOR haploinsufficiency corresponded to a significant hypo‐expression in t(X;21) cases, compared to normal controls and to normal karyotype AML. By contrast, RUNX1 expression was not altered, suggesting a compensatory effect by the remaining allele. Whole transcriptome analysis showed that overexpression of HOXA9 differentiated t(X;21) from both controls and t(8;21)‐positive AML. In conclusion, we characterized a new recurrent reciprocal t(X;21)(p11.4;q22.12) chromosome translocation in MDS and AML, generating simultaneous BCOR and RUNX1 deletions rather than a fusion gene at the genomic level.