Cytogenomic Characterization of Double Minute Heterogeneity in Therapy Related Acute Myeloid Leukemia

Publication date: Available online 6 August 2019Source: Cancer GeneticsAuthor(s): Prasad Koduru, Weina Chen, Barbara Haley, Kevin Ho, Dwight Oliver, Kathleen WilsonAbstractBreast cancer patients treated with adjuvant chemotherapy regimens containing alkylating agents and anthracyclines are at an increased risk for secondary myeloid malignancies, either acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Complex genomic changes (karyotypes and/or gene amplification) accompany the development of the secondary neoplasms. Here we present a unique case of a breast cancer patient who developed secondary AML within 18 months of treatment with trastuzumab, pertuzumab, docetaxel, carboplatin (TCHP) and radiation. Leukemia cells had catastrophic alterations in chromosomes 8, 11, and 17. Concurrent genetic abnormalities in the leukemia cells included amplification of MYC and KMT2A, and deletion and mutational inactivation of TP53. MYC and KMT2A amplified at different levels and on different double minutes, which we called as double minute heterogeneity. Clinically, this case highlights the need to identify genes amplified in secondary myeloid malignancies by cytogenomic microarray (CMA) analysis since these may have therapeutic implications.
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research