4.16 Identification of Minor Proportion p53 Mutations Selected Later by Therapy

Abstract

fixed cell pellet) were re-scored for % abnormal nuclei among 200 consecutive round nuclei. Scores were compared to the original clinical FISH analyses (200 consecutive nuclei not selected for nuclear morphology). Results: After re-scoring by the round cell approach, 12 originally normal samples remained normal while 16 (57%) were abnormal. The average number of days between the diagnostic and follow-up sample was 826 for those that remained normal and 601 for those abnormal by scoring round cells only. In one case, 12 had originally been scored in 0.5% but round cell approach showed 10% 12. Another 2 previously normal cases with the unusual combination of 11qand 17pbecame abnormal by the round cell approach. Among previously normal samples, 3 were abnormal for multiple FISH probes by the round cell approach and 13 were abnormal for 1 FISH probe. Discussion: The present experiment shows, as in our past study, that abnormal CLL FISH patterns are confined to round nuclei. Thus, utilization of the round cell approach for scoring FISH in CLL increases the sensitivity to detect a genetic defect. We believe restricting CLL FISH panel scoring to the leukemic B-cell population will be a powerful adjunct to cytogenetic analysis for CLL patients with low lymphocyte counts, including those in clinical remission or with minimal residual disease.