Chromosome 13q14 deletions in Multiple Myeloma at Chris-Hani Baragwanath Hospital
Date
2010-09-17
Authors
Pheeha, Sekgokwa Teboho Stella
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Abstract
Multiple Myeloma (MM) is a malignancy of plasma cells. The incidence worldwide has been reported to be 3-4/100 000 of the population. The exact aetiology is not known, but several factors have been implicated in the aetio-pathogenesis of the disease.
Chromosomal abnormalities are well documented in MM. Their detection is important, as some of the cytogenetic abnormalities such as the 13q deletion are associated with a poor prognosis. Knowledge of the prognostic factors guides the clinician with respect to the appropriate management of the patient.
Prior to the use of fluorescence in situ hybridisation (FISH) as a technique for detecting cytogenetic abnormalities in MM, progress was slow in this field because of the difficulty of obtaining analysable metaphases in view of the low proliferative activity of plasma cells. FISH has significantly improved the detection rate over conventional cytogenetics.
Objective: The present study set out to determine the proportion of patients with MM who have a detectable chromosome 13q deletion using conventional cytogenetic and FISH analysis. The FISH technique was specifically studied to see if the detection rate of the 13q deletion is improved compared to conventional cytogenetics. Furthermore, the cytogenetic abnormalities detected were correlated with the course of the disease, as well as other parameters of prognostic significance.
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Methods: Bone marrow aspiration specimens were obtained from thirty (30)
patients with MM. Both newly and previously diagnosed patients were
included.
The sample size was however reduced to twenty (20) because of the
need to optimise the technique and improve signal detection.
Conventional cytogenetic and FISH analysis was performed using the LSI D13S319 DNA probe as the test probe, and the centromeric alpha 11 and 18 as control probes. The analysis was carried out by two observers.
Results: In the current study, the detection of chromosomal aberrations was much better with FISH analysis compared to conventional cytogenetics i.e. 25% versus 5%.
Of all the patients with chromosomal aberrations, 25% (5/20) had the specific deletion 13q14 (D13S319). Most of our patients (70%) presented with stage III disease. 60% of those were positive for deletion 13q14 (D13S319), i.e 3/5 patients had stage III disease. However, there was no correlation between disease stage and chromosome status, as the majority of the patients presented with advanced stage disease, irrespective of their chromosomal status. Other factors of prognostic significance such as the haemoglobin level, beta-2 microglobulin and creatinine levels were not found to correlate with the presence of the chromosomal aberration but with disease stage. Furthermore, median survival did not correlate with the presence of the chromosomal abnormality.
Conclusion: FISH analysis improves the detection rate of chromosomal abnormalities in MM compared to conventional cytogenetics. The prevalence of 13q14 deletion in our patient population is lower than that reported in the
Description
MMed (Haematology), Faculty of Health Sciences, University of the Witwatersrand
Keywords
FISH analysis, chromosomal abnormalities, multiple myeloma