Cryptic recurrent ACIN1-NUTM1 fusions in non-KMT2A-rearranged infant acute lymphoblastic leukemia.
| Title: | Cryptic recurrent ACIN1-NUTM1 fusions in non-KMT2A-rearranged infant acute lymphoblastic leukemia. |
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| Authors: | Pincez T; Pediatric Hematology-Oncology Division, Charles-Bruneau Cancer Center, CHU Sainte-Justine, Montréal, Québec, Canada.; Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.; Landry JR; Pediatric Hematology-Oncology Division, Charles-Bruneau Cancer Center, CHU Sainte-Justine, Montréal, Québec, Canada.; Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.; Streamline Genomics, Montréal, Québec, Canada.; Roussy M; Pediatric Hematology-Oncology Division, Charles-Bruneau Cancer Center, CHU Sainte-Justine, Montréal, Québec, Canada.; Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.; Department of Biomedical Sciences, Université de Montréal, Montréal, Québec, Canada.; Jouan L; Integrated Centre for Pediatric Clinical Genomics, CHU Sainte-Justine, Montréal, Québec, Canada.; Bilodeau M; Pediatric Hematology-Oncology Division, Charles-Bruneau Cancer Center, CHU Sainte-Justine, Montréal, Québec, Canada.; Laramée L; Pediatric Hematology-Oncology Division, Charles-Bruneau Cancer Center, CHU Sainte-Justine, Montréal, Québec, Canada.; Couture F; Molecular Diagnostic Laboratory, CHU Sainte-Justine, Montréal, Québec, Canada.; Sinnett D; Pediatric Hematology-Oncology Division, Charles-Bruneau Cancer Center, CHU Sainte-Justine, Montréal, Québec, Canada.; Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.; Gendron P; Bioinformatics Core Facility, Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada.; Hébert J; Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.; Division of Hematology, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada.; Quebec Leukemia Cell Bank, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada.; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada.; Oligny L; Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.; Department of Pathology, CHU Sainte-Justine, Montréal, Québec, Canada.; Rouette A; Integrated Centre for Pediatric Clinical Genomics, CHU Sainte-Justine, Montréal, Québec, Canada.; Tran TH; Pediatric Hematology-Oncology Division, Charles-Bruneau Cancer Center, CHU Sainte-Justine, Montréal, Québec, Canada.; Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.; Wilhelm BT; Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada.; Laboratory for High Throughput Biology, IRIC, Université de Montréal, Montréal, Québec, Canada.; Bittencourt H; Pediatric Hematology-Oncology Division, Charles-Bruneau Cancer Center, CHU Sainte-Justine, Montréal, Québec, Canada.; Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.; Cellot S; Pediatric Hematology-Oncology Division, Charles-Bruneau Cancer Center, CHU Sainte-Justine, Montréal, Québec, Canada.; Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.; Quebec Leukemia Cell Bank, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada. |
| Source: | Genes, chromosomes & cancer [Genes Chromosomes Cancer] 2020 Feb; Vol. 59 (2), pp. 125-130. Date of Electronic Publication: 2019 Oct 04. |
| Publication Type: | Case Reports; Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Wiley-Liss Country of Publication: United States NLM ID: 9007329 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-2264 (Electronic) Linking ISSN: 10452257 NLM ISO Abbreviation: Genes Chromosomes Cancer Subsets: MEDLINE |
| Imprint Name(s): | Publication: New York, NY : Wiley-Liss; Original Publication: New York : A.R. Liss, c1989- |
| MeSH Terms: | Neoplasm Proteins/*genetics ; Nuclear Proteins/*genetics ; Oncogene Proteins, Fusion/*genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics; Gene Rearrangement/genetics ; Histone-Lysine N-Methyltransferase/genetics ; Histone-Lysine N-Methyltransferase/metabolism ; Leukemia, Myeloid, Acute/genetics ; Myeloid-Lymphoid Leukemia Protein/genetics ; Myeloid-Lymphoid Leukemia Protein/metabolism ; Neoplasm Proteins/metabolism ; Nuclear Proteins/metabolism ; Oncogene Proteins, Fusion/metabolism ; Chromosome Aberrations ; Cytogenetics ; Gene Fusion ; Humans ; Immunohistochemistry ; Infant, Newborn ; Male |
| Abstract: | 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.; (© 2019 Wiley Periodicals, Inc.) |
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| Contributed Indexing: | Keywords: NUTM1; acute lymphoblastic leukemia; gene fusion; infant leukemia; minimal residual disease; transcriptomics |
| Substance Nomenclature: | 0 (ACIN1 protein, human); 0 (KMT2A protein, human); 0 (NUTM1 protein, human); 0 (Neoplasm Proteins); 0 (Nuclear Proteins); 0 (Oncogene Proteins, Fusion); 149025-06-9 (Myeloid-Lymphoid Leukemia Protein); EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) |
| Entry Date(s): | Date Created: 20190914 Date Completed: 20200416 Latest Revision: 20200416 |
| Update Code: | 20260130 |
| DOI: | 10.1002/gcc.22808 |
| PMID: | 31515871 |
| Database: | MEDLINE |
Case Reports; Journal Article; Research Support, Non-U.S. Gov't