Comparison of Diagnostic Yield of a FISH Panel Against Conventional Cytogenetic Studies for Hematological Malignancies: A South Indian Referral Laboratory Analysis Of 201 Cases

Vishal Ashok, Ramya Ranganathan, Smitha Chander, Sharat Damodar, Sunil Bhat, Nataraj K S, Satish Kumar A, Sachin Suresh Jadav, Mahesh Rajashekaraiah, Sundareshan T S, Vishal Ashok, Ramya Ranganathan, Smitha Chander, Sharat Damodar, Sunil Bhat, Nataraj K S, Satish Kumar A, Sachin Suresh Jadav, Mahesh Rajashekaraiah, Sundareshan T S

Abstract

Objectives: Genetic markers are crucial fort diagnostic and prognostic investigation of hematological malignancies (HM). The conventional cytogenetic study (CCS) has been the gold standard for more than five decades. However, FISH (Fluorescence in Situ Hybridization) testing has become a popular modality owing to its targeted approach and the ability to detect abnormalities in non-mitotic cells. We here aimed to compare the diagnostic yields of a FISH panel against CCS in HMs. Methods: Samples of bone marrow and peripheral blood for a total of 201 HMs were tested for specific gene rearrangements using multi-target FISH and the results were compared with those from CCS. Results: Exhibited a greater diagnostic yield with a positive result in 39.8% of the cases, as compared to 17.9% of cases detected by CCS. Cases of chronic lymphocytic leukaemia (CLL) benefited the most by FISH testing, which identified chromosomal aberrations beyond the capacity of CCS. FISH was least beneficial in myelodysplastic syndrome (MDS) where the highest concordance with CCS was exhibited. Acute lymphocytic leukaemia (ALL) demonstrated greater benefit with CCS. In addition, we found the following abnormalities to be most prevalent in HMs by FISH panel testing: RUNX1 (21q22) amplification in ALL, deletion of D13S319/LAMP1 (13q14) in CLL, CKS1B (1q21) amplification in multiple myeloma and deletion of EGR1/RPS14 (5q31/5q32) in MDS, consistent with the literature. Conclusions: In conclusion, FISH was found to be advantageous in only a subset of HMs and cannot completely replace CCS. Utilization of the two modalities in conjunction or independently should depend on the indicated HM for an optimal approach to detecting chromosomal aberrations.

Keywords: Chromosomal aberration; cytogenetics; fluorescence in situ hybridization; hematological malignancies.

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Figures

Figure 1
Figure 1
Graph Showing Percentage of Group 1 (concordance between the two modalities), Group 2 (FISH advantageous) and Group 3 (CCS advantageous). X-axis: Sample size (%), Y-axis: Individual HMs.
Figure 2
Figure 2
Graphical Representation of CA Picked up by FISH in HM, X-axis: Chromosomal Aberration targeted by specific FISH probe, Y-axis: Incidence in percentage within FISH positive sample group
Figure 3
Figure 3
Signal Pattern for Select FISH Probes Included; A: BCR/ABL double fusion (1G1R2Y), B: 3 copies of ABL (3R), C: Single fusion of BCR/ABL with ABL deletion (2G1R1Y), D: Atypical ETV6/RUNX1 fusion indicating 3-way translocation (1Y2G2R), E: RUNX1 amplification (2R4G), F. ETV6 deletion (1R2G), G. Hemizygous deletion of D13S319(2B1R), H. Monosomy 13 (1R1B), I. Trisomy 12 (3G), J. CKS1B amplification (5R), K. IGH break apart (1Y1R1G), L. Trisomy 8 (3B)

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