Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q-

Abstract

BackgroundMore than 50% of patients with myelodysplastic syndromes present cytogenetic aberrations at diagnosis. Partial or complete deletion of the long arm of chromosome 5 is the most frequent abnormality. The aim of this study was to apply fluorescence in situ hybridization of 5q31 in patients diagnosed with de novo myelodysplastic syndromes in whom conventional banding cytogenetics study had shown a normal karyotype, absence of metaphases or an abnormal karyotype without evidence of del(5q). Design and MethodsWe performed fluorescence in situ hybridization of 5q31 in 716 patients, divided into two groups: group A patients (n=637) in whom the 5q deletion had not been detected at diagnosis by conventional banding cytogenetics and group B patients (n=79), in whom cytogenetic analysis had revealed the 5q deletion (positive control group). ResultsIn group A (n=637), the 5q deletion was detected by fluorescence in situ hybridization in 38 cases (5.96%). The majority of positive cases were diagnosed as having the 5q-syndrome. The deletion was mainly observed in cases in which the cytogenetics study had shown no metaphases or an aberrant karyotype with chromosome 5 involved. In group B (n=79), the 5q deletion had been observed by cytogenetics and was confirmed to be present in all cases by fluorescence in situ hybridization of 5q31. ConclusionsFluorescence in situ hybridization of 5q31 detected the 5q deletion in 6% of cases without clear evidence of del(5q) by conventional banding cytogenetics. We suggest that fluorescence in situ hybridization of 5q31 should be performed in cases of a suspected '5q-syndrome' and/or if the cytogenetic study shows no metaphases or an aberrant karyotype with chromosome 5 involved (no 5q-chromosome).

Cytogenetic follow-up by karyotyping and fluorescence in situ hybridization: implications for monitoring patients with myelodysplastic syndrome and deletion 5q treated with lenalidomide

“…6 In the literature, several studies described discrepant results of karyotype and FISH analyses. 10,[14][15][16][17] In most instances, the cases with a discrepant result (positive by FISH only) had an insufficient number of metaphases or the chromosome morphology was poor. Pitchford et al recommended FISH in myelodysplastic syndrome patients only if an adequate karyotyping with at least 20 metaphases was not possible, since they were unable to demonstrate any advantage of FISH in the setting of an optimal banding analysis.…”

Standardized fluorescence in situ hybridization testing based on an appropriate panel of probes more effectively identifies common cytogenetic abnormalities in myelodysplastic syndromes than conventional cytogenetic analysis: A multicenter prospective study of 2302 patients in China

“…Several studies have demonstrated that the combination of FISH and CC analysis significantly improved the detection of abnormalities in the cytogenetic diagnosis of MDS [4][5][6][7][8][9][10][11]. Conversely, other studies have reported that FISH detected 6% or fewer additional abnormalities compared to CC analysis alone, and these studies suggested limiting FISH testing to cases with suboptimal karyotyping [12][13][14][15][16][17][18]. The examination of small sample sizes and the use of data collected from a single center might have contributed to these differing results.…”

“…However, the clinical role of FISH studies and the context in which FISH might provide additional information that is undetectable by CC analysis remain uncertain. Prior studies comparing CC and FISH panel testing in MDS have yielded conflicting results [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Several studies have demonstrated that the combination of FISH and CC analysis significantly improved the detection of abnormalities in the cytogenetic diagnosis of MDS [4][5][6][7][8][9][10][11].…”

“…Fluorescence in situ hybridization (FISH), which does not require dividing cells and can be easily quantified, is increasingly being used to identify specific cytogenetic aberrations in MDS [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. The primary advantage of FISH is its greater sensitivity than CC analysis, resulting from the analysis of a greater number of interphase cells.…”

Patients with del(5q) MDS who fail to achieve sustained erythroid or cytogenetic remission after treatment with lenalidomide have an increased risk for clonal evolution and AML progression

“…Cytogenetic investigation should always include full karyotype analyses, since in many patients loss of cytogenetic response was indicated by only one metaphase with 5q deletion, whereas FISH analysis provided a negative result. Thus, FISH using a probe for the commonly deleted region in 5q [24] does not seem to be sufficient for follow-up analysis. Our results underline the importance of a close and careful cytogenetic follow-up even after reaching a CCyR, since the clone with 5q deletion may reappear, increase in size and acquire additional chromosome aberrations, indicating progression of the disease.…”