Abstract
Introduction: Clonal chromosomal aberrations (CCAs) convey a recurrent genetic change derived from a single evolving clone. CCAs have been identified in various cancers including hematological malignancies. However, those found in hematopoietic cells have not been well studied in cytopenic patients without hematological malignancies. In addition, clinical meanings of non-clonal chromosomal aberrations (NCCAs) are being revisited in genetic research of clinical oncology.
Purpose: To elucidate the prevalence and clinical outcome of CCA/NCCA in cytopenic patients without hematological malignancies, we investigated chromosomal aberrations of patients' bone marrow samples.
Methods: We reviewed 253 consecutive patients who underwent bone marrow aspiration to examine the cause of cytopenia at our institute between 2012 and 2015. The final diagnosis was determined by more than two hematologists/specialists. Patients diagnosed with hematological malignancies were excluded from this study. CCA was defined as chromosomal aberrations detected in at least two cells by chromosomal studies of 20 cells, whereas NCCA was defined as a chromosomal aberration detected in only a single cell.
Results: A total of 253 bone marrow samples were evaluated (117 females). The median age was 66 years (range, 1-92 years). Patients without hematological malignancies were 133 (68 females) with the median age of 64 years (range, 1-92 years), of whom 27 (20.0%; median, 69 years; range, 54-81 years; 8 females) harbored chromosomal aberrations. CCA was detected in 14 patients. The most leading CCA was -Y in eight patients. Other CCAs identified were inv(9) in three patients, followed by mar1+, inv(12), and t(19;21) in 1 patient each. NCCAs were detected in 13 patients. The most leading NCCA was +Y in four patients, followed by del(20), +8, inv(2), -8, and add(6) in 1 patient each. Non-clonal translocation abnormalities, including t(9;14), t(14;16), and t(13;21), were observed in three patients; these were suggestive but did not lead to specific malignancies. One patient had a complex karyotype in a single cell. We used the remaining 106 patients with normal karyotype as a control group (median, 65 years; range, 1-92 years; 56 females). A follow-up study revealed that the overall survival of the NCCA group was the poorest compared with that of the other two groups with CCA or normal karyotype (Figure 1, P < 0.0001; log-rank test).
Conclusion: Our study reveals that chromosomal aberration is commonly observed in cytopenic patients without hematological malignancies (20.3%; 27/133). CCAs were observed in 10.5% (14/133) and NCCAs were observed in 9.8% (13/133) of patients. In our consecutive cohort, the latter group of patients demonstrated lower survival rate than the patients harboring normal karyotype or CCA. NCCAs are still considered by many to be an in vitro culture artifact; however, the clinical outcome of patients with NCCA in our study correlates with the recent concept of NCCA as clinically meaningful nonrecurrent changes [Genes 2017; 8: 155]. Although NCCAs do not indicate clonal expansion from a single common ancestor, it can be a reliable marker of genetic instability. Hence, a long-term follow-up should be considered even for patients with NCCA.
No relevant conflicts of interest to declare.
