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Cryptic recurrent ACIN1 ‐ NUTM1 fusions in non‐ KMT2A ‐rearranged infant acute lymphoblastic leukemia
Author(s) -
Pincez Thomas,
Landry JosetteRenée,
Roussy Mathieu,
Jouan Loubna,
Bilodeau Mélanie,
Laramée Louise,
Couture Françoise,
Sinnett Daniel,
Gendron Patrick,
Hébert Josée,
Oligny Luc,
Rouette Alexandre,
Tran Thai H.,
Wilhelm Brian T.,
Bittencourt Henrique,
Cellot Sonia
Publication year - 2020
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22808
Subject(s) - minimal residual disease , biology , fusion gene , fusion transcript , gene rearrangement , transcriptome , exon , gene , leukemia , genetics , cancer research , gene expression
Infant acute lymphoblastic leukemias (ALL) are rare hematological malignancies occurring in children younger than 1 year of age, most frequently associated with KMT2A rearrangements ( KMT2A ‐r). The smaller subset without KMT2A ‐r, which represents 20% of infant ALL cases, is poorly characterized. Here we report two cases of chemotherapy‐sensitive non‐ KMT2A ‐r infant ALL. Transcriptome analyses revealed identical ACIN1‐NUTM1 gene fusions in both cases, derived from cryptic chromosomal rearrangements undetected by standard cytogenetic approaches. Two isoforms of the gene fusion, joining exons 3 or 4 of ACIN1 to exon 3 of NUTM1 , were identified. Both fusion transcripts contained the functional DNA‐binding SAP (SAF‐A/B, Acinus, and PIAS) domain of ACIN1 and most of NUTM1 . The detection of the ACIN1‐NUTM1 fusion by RT‐PCR allowed the molecular monitoring of minimal residual disease in a clinical setting. Based on publicly available genomic datasets and literature review, we predict that NUTM1 gene fusions are recurrent events in infant ALL. As such, we propose two clinically relevant assays to screen for NUTM1 rearrangements in bone marrow cells, independent of the fusion partner: NUMT1 immunohistochemistry and NUTM1 RNA expression. In sum, our study identifies ACIN1 ‐ NUTM1 as a recurrent and possibly cryptic fusion in non‐ KMT2A ‐r infant ALL, provides clinical tools to screen for NUTM1 ‐rearranged leukemia and contributes to the refinement of this new subgroup.