The Genetic Abnormalities Of Multiple Yeloma And Their Significance Detecting By Fluorescence In Situ Hybridization

Objective To explore the genetic abnormalities and its clinical significance of multiple myeloma patients detected by fluorescence in situ hybridization(FISH).Method With the application of fluorescence in situ hybridization(FISH),sequence specific DNA probes( IgH , RB1, D13S319, p53 and 1q21) were applied to detect 14q32 rearrangement, del(13q14), del(17p13) and gain of 1q21. Forty-four MM patients were enrolled in this study. The threshold was established using 10 controls without hematopoietic malignancies. Meanwhile its results were compared with that of conventional cytogenetic G banding,and the clinical implications of chromosomal abnormalities were investigated.Results(1) FISH technique detected 32 cases(72.7%) of genetic abnormality in 44 cases,1q21 amplification was observed in 11 (25.0% ) cases ,RB1 deletion was observed in 17(38.6%) cases,D13s319 deletion was observed in 16(36.4%)cases,p53 deletion was observed in 6 (13.6%) cases,14q32 translocation was observed in 19 (43.2% ) cases; One abnormality detected in 10 cases (22.7%), two abnormalities in 11 cases (25.0%), three abnormalities in 8 cases (18.2%), 4 kinds of abnormalities in 3 cases (6.8%) .(2) From 44 patients, 28 can detect split-phase by conventional cytogenetic and 2 cases (7.14%) with abnormalities. Genetic abnormalities detected by conventional G-banding positive rate was 7.14%, while FISH positive rate was 72.7%, the difference was significant (p<0.05). (3) Genetic abnormalities compared with clinical parameters showed that,β2-MG in IGH abnormal patients were significantly higher than without such abnormalities (P<0.05).Bone marrow plasma cells of 1q21 amplification patients were higher than those with normal karotypes(P<0.05), CRE was significantly higher among 1q21 amplification and P53 deletion patients (P<0.05). CRP was significantly higher among P53 deletion patients (P<0.05)(4) By the age <50 years old ,50-70 years old,> 70 years old gene abnormalities were detected in 2 cases (50.0%), 26 cases (74.3%), 4 patients (80%). The three groups of genetic abnormalities by chi-square test have no significant difference (P>0.05).(5) Chromosome aberration and stage have not significant differences in relationship (P>0.05), but the genetic abnormalities were more in typeⅢand IgG-based.Conclusion Chromosome complex aberration is the mainly cytogenetic characteristic of multiple myeloma, where numerical or structural aberrations are involved. For patients with multiple myeloma, FISH can detect more abnormal karyotype than conventional G-banding chromosome analysis. The study shows that the most common genetic abnormality is IGH gene rearrangement and absence of RB1 and D13S319, followed by 1q21 amplification, P53 deletion at least.The sample size was too small to perform a meaningful statistical test.To vertify this hypothesis,an expanded sample size was required. Less patients treated with regular treatment and we did not get a meaningful cytogenetic changes and survival time in comparison, so need further studies with larger sample. FISH is suggested for patients at diagnosis and during the disease progression to evaluate the prognosis.