Acute leukemias harboring KMT2A/MLLT10 fusion: a 10‐year experience from a single genomics laboratory

Autor: Beth A. Pitel, William R. Sukov, Nicole L. Hoppman, Reid G. Meyer, Kathryn E. Pearce, Rhett P. Ketterling, Linda B. Baughn, Patricia T. Greipp, Jess F. Peterson, George Vasmatzis, Stephanie A. Smoley, Cynthia M. Williamson, James B. Smadbeck
Rok vydání: 2019
Předmět:
Male
Oncology
Cancer Research
medicine.medical_specialty
Oncogene Proteins
Fusion
Biopsy
Sensitivity and Specificity
03 medical and health sciences
0302 clinical medicine
Internal medicine
Biomarkers
Tumor
Genetics
medicine
Myeloid sarcoma
Humans
Genetic Predisposition to Disease
Genetic Testing
Gene
Genetic Association Studies
In Situ Hybridization
Fluorescence
Retrospective Studies
biology
medicine.diagnostic_test
Infant
Newborn
Chromosome Mapping
Infant
Reproducibility of Results
Myeloid leukemia
Chromosome
Histone-Lysine N-Methyltransferase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
medicine.disease
Lymphoma
Leukemia
Myeloid
Acute
Leukemia
KMT2A
030220 oncology & carcinogenesis
biology.protein
Female
Myeloid-Lymphoid Leukemia Protein
Transcription Factors
Fluorescence in situ hybridization
Zdroj: Genes, Chromosomes and Cancer. 58:567-577
ISSN: 1098-2264
1045-2257
Popis: The MLLT10 (formerly AF10) gene is the fourth most common KMT2A fusion partner across all acute leukemias and requires at least 3 breaks to form an in-frame KMT2A/MLLT10 fusion due to the opposite orientation of each gene. A 10-year retrospective review was performed to identify individuals from all age groups that harbor KMT2A/MLLT10 fusion obtained by our KMT2A/MLLT10 dual-color dual-fusion fluorescence in situ hybridization (D-FISH) assay. Of the 60 unique individuals identified, 31 were male and 29 were female (M:F ratio, 1.1:1) with ages ranging from 3 days to 86 years (mean 21.5 years, median 5.5 years). The diagnoses included acute myeloid leukemia (AML) (49 patients, 82%), B- or T-lymphoblastic leukemia/lymphoma (7 patients, 12%), myeloid sarcoma (3 patients, 5%), and a single case (2%) of undifferentiated leukemia. Twenty-seven of 49 patients (55%) with AML were in the infant or pediatric age group. Fifty-three of 60 patients (88%) had KMT2A/MLLT10 D-FISH signal patterns mostly consisting of single fusions. In addition, 10 (26%) of 38 patients with conventional chromosome studies had "normal" (5 patients) or abnormal (5 patients) chromosome studies that lacked structural or numeric abnormalities involving chromosomes 10 or 11, implying cryptic cytogenetic mechanisms for KMT2A/MLLT10 fusion. Lastly, mate-pair sequencing was performed on 4 AML cases, 2 of which had "normal" chromosome studies and cryptic KMT2A/MLLT10 fusion as detected by KMT2A/MLLT10 D-FISH studies, and verified the multiple breaks required to generate KMT2A/MLLT10 fusion.
Databáze: OpenAIRE
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