Signature OncoChip™ | Copy Number Evaluation
Clinical Vignette
Progression of myelodysplastic syndrome**
A 58-year-old male patient presented with reports of fatigue, dyspnea, and palpitations. His initial blood workup identified anemia. Subsequent pathology consultation identified 5% blasts in bone marrow, resulting in a classification of refractory anemia with excess blasts-1 (RAEB-1). Knowing that cytogenetic studies can better classify prognosis for patients with myelodysplastic syndromes (MDS), the pathologist ordered a karyotype and the OncoChip™ | Copy Number Evaluation.3
The OncoChip™ | Copy Number Evaluation results, reported on the 5th day after specimen receipt in the laboratory, identified three clinically significant aberrations, including deletion 5q, trisomy 21, and a 380 kilobase deletion of the RUNX1 gene. Karyotyping results, completed five days after the OncoChip™ | Copy Number Evaluation, showed the large aberrations resulting in a karyotype of 46,XY,del(5)(q13q33)[11]/47,idem,+21[13]. Because the chromosome resolution was not sufficient to identify a small deletion and FISH for RUNX1 was not performed on the specimen, the deletion was not identified.
Patients with MDS who are younger than 60 at diagnosis, have anemia but no other cytopenias, and present with RAEB-1 in the absence of cytogenetic information have a low- to intermediate-risk disease state.3 Additionally, 5q- is considered a good prognostic marker when seen in isolation, although when seen in combination with other cytogenetic abnormalities the prognosis becomes poorer as the number of abnormalities increase.3 Presence of 2 cytogenetic abnormalities including 5q- classifies the disease as having an intermediate prognosis. RUNX1 deletion, which was not detected by karyotype or FISH in this patient, has been reported in MDS patients at the time of transformation to acute myeloid leukemia (AML).4
The presence of this deletion changed this patient’s prognosis from an intermediate-level prognosis to identification of immediate disease evolution and therefore indicated that more intensive therapy, such as stem-cell transplant, should be considered.2,3 Furthermore, some patients with RUNX1 deletions have a family history of familial platelet disorder with propensity to AML, and therefore family history of this patient should be considered to evaluate risk for other family members.1
The quick turn-around time and high-resolution of the OncoChip™ | Copy Number Evaluation provided prognostically significant cytogenetic results more quickly than standard karyotyping and provided additional prognostic information that karyotyping could not, allowing the clinician to significantly modify therapy for this patient and to potentially provide important risk information to this patient’s family.
Figure 1. OncoChip™ | Copy Number Evaluation showing trisomy 21 and concurrent RUNX1 deletion. The top shows an ideogram of chromosome 21 with the proximal q-arm to the left and the distal q-arm to the right. The section of chromosome indicated in red is expanded to show the plot of array CGH data for the entire q-arm. The pink highlighted area within the plot indicates a gain of the entire q-arm, consistent with trisomy 21. The blue highlighted area within the plot shows a submicroscopic deletion involving RUNX1.
References:
- Béri-Dexheimer et al. 2008. Eur J Hum Genet. 16:1014-8.
- Deeg et al. 2002. Blood. 100:1201-7.
- Greenberg et al. 1997. Blood. 89:2079-88.
- Slovak et al. 2010. Mol Cytogenet. 3:23.
* This assay is not designed to detect low level mosaicism.
** This vignette is based upon a real patient, however specific details have been changed to demonstrate utility of the platform and protect patient privacy.