Dr. Spiteri is a board-certified Cytogeneticist and Molecular Geneticist, Director of Cytogenetics and Co-Director of Clinical Genomics at Stanford Medicine. Dr. Spiteri’s research focuses on identifying novel gene-disease relationships in constitutional disorders and expanding our understanding of the genetics of hematological disorders by investigating abnormalities of uncertain significance in these areas to elucidate the underlying pathogenesis.
Elizabeth Spiteria, Leena Borkarb, Jason Erdmannb, Tian Zhangc, Jyoti Kumara
aStanford Medicine, Palo Alto, CA, USA; bStanford Healthcare, Palo Alto, CA, USA; cCancer Institute, Stanford University, Palo Alto, CA, USA
Chromosome analysis is a first-line ancillary test performed on bone marrows to evaluate for hematopoietic malignancy. While characteristic cytogenetic findings correlate with pathology in most cases, the chromosomal abnormalities are sometimes too complex for complete characterization, limiting interpretation of the results. Additionally, chromosomal abnormalities may lack correlation with the hematopathology findings. Here, we present two cases where chromosomal microarray was performed, which aided interpretation of chromosome analysis.
Case 1: A patient with a history of acute myeloid leukemia (AML) with NPM1 mutation had a bone marrow evaluated for residual disease. Although chromosome analysis identified a mosaic balanced translocation between chromosomes 7 and 17, concurrent ancillary studies were unrevealing. The significance of this finding was unclear given the unremarkable morphology and flow cytometry. Chromosomal microarray identified deletions of NF1 and SUZ12 on chromosome 17 as well as deletion of ASXL1 on chromosome 20, which may be a driver for leukemogenesis in this case.
Case 2: A patient presented with circulating blasts and was diagnosed with AML. Chromosome analysis demonstrated deletion of chromosome 5q and loss of chromosome 7. However, additional complex chromosomal abnormalities were also identified, including a jumping translocation. Chromosomal microarray showed complex abnormalities of chromosome 1p, gain of chromosome 5p including TERT and IL7R, deletion of IKZF1 on chromosome 7, and deletion of TP53 on chromosome 17. These chromosomal microarray findings provide greater insight toward AML pathogenesis.
These case reports demonstrate the utility of chromosomal microarray in further defining chromosomal findings with unclear significance to further understand disease pathogenesis.