The Clonal Fraction of MDS Cells in Standard Clinical Specimens: Implications for the Application of Array CGH Methods for Prognostic Studies
M Kristina Subik, Nancy Wang, W Richard Burack. University of Rochester Medical Center, Rochester, NY
Background: The cytogenetics of MDS within the neoplastic bone marrow cells is essential for determining prognosis. G-banding (karyotype) and FISH are the most commonly performed analyses. Microarray CGH is increasingly being performed.
Design: 2934 sequential cases accessioned with an indication of MDS over 4 years were studied by G-banding and FISH. FISH was performed for 5 lesions with defined prognostic significance, -5/del5q, -7/del7q, +8, del20q.
Results: G-banding with 1-20 metaphases was obtained on 2507/2934 cases; all cases were available for FISH analysis on 200 interphase nuclei. A genomic aberration was detected by karyotype in 1174/2507 (47%). In contrast, FISH detected aberrations in 422/2934 (14%) cases. FISH detected the following MDS-associated abnormalities: del5q (54 cases), -7 (25 cases), del7q(20 cases), +8(63 cases), del20q(51 cases). Karyotype failed to detect many of the cases with abnormalities seen by FISH (13% del5q; 27% -7, 30% del7q, 40% +8, 38% del20q). In contrast, aberrations were found in only 1 case by karyotype that was not also identified by FISH. Discordance rates varied with the number of metaphase spreads available: 25 cases with FISH abnormalities were seen in 1771 cases with 20 normal metaphase spreads (1.4%) while 49 cases with FISH abnormalities were in 332 cases with all normal metaphase spreads (15%) but for which 20 metaphases could not be obtained. To explore the possible application of array CGH as a substitute for FISH, we assessed the clonal fraction of MDS cells. Based on literature review, we assume that 20% is a reasonable minimal clonal fraction needed for detection in clinical applications for array methods. 95/213 (45%) FISH abnormalities were present at a frequency of ≤20% (del5q 28%; -7 40%; del7q 30%; +8, 57%; del20q, 55%).
Conclusions: If 20 metaphase spreads can be obtained, FISH has little added utility but if 20 metaphase spreads are not obtained, the value of performing FISH is high. Assuming that array CGH methods require a 20% clonal fraction for detection, 45% of lesions having defined prognostic significance in MDS would go undetected if microarray was the sole method.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 171, Tuesday Morning