Frequency and distribution of trisomy 11 in multiple myeloma patients: relation with overexpression of CCND1 and t(11;14).
Multiple myelomas (MM) recently have been stratified into five groups (TC1-TC5) on the basis of the presence of the recurrent IgH chromosomal translocation and cyclin D expression. Cyclin D1 is detectable in up to one third of MM patients and plays crucial role in the regulation of G1-S transition in cell cycle. To evaluate the mechanisms of cyclin D1 overexpression, fluorescence in situ hybridization analysis with specific probes for the CCND1 gene and t(11;14)(q13;q32) were performed on highly purified plasma cells from bone marrow samples of 30 MM patients at diagnosis. CCND1 gene overexpression was detected in 14/30 cases (46.6%). Patients with evidence of the t(11;14) showed strong nuclear staining for cyclin D1 (TC1 group) and 7/8 demonstrated CCND1 overexpression. The remaining 7/15 cases with increased CCND1 gene copy numbers lacked the t(11;14) and showed low to negative levels of cyclin D1 protein (TC2 group). Trisomy 11 was demonstrated in 2/8 cases carrying the t(11;14) (TC1), 6/7 overexpressing cyclin D1 without the translocation (TC2), and 4/15 negative for both alterations (TC3-TC5). According to our data, trisomy 11 does not appear to directly cause CCND1 gene overexpression because it was present in 4/15 patients without the overexpression of the CCND1 gene and in 2/8 patients carrying the t(11;14). One patient belonging to the TC2 group overexpressed cyclin D1 and lacked both trisomy and translocation, suggesting that cyclin D1 can be dysregulated by additional mechanisms. In the TC2 group, trisomy 11 may probably be considered as a recurrent polisomy of the hyperdiploid status.
Guglielmelli
Tommasina
T
Department of Clinical and Biological Sciences, University of Turin and St. Luigi Hospital, Regione Gonzole 10, 10043 Orbassano, Turin, Italy. tgugliemelli@libero.it
Giugliano
Emilia
E
Cappia
Susanna
S
Papotti
Mauro
M
Saglio
Giuseppe
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D056741:Cyclin D; D016213:Cyclins / Q000032:analysis / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic; D014314:Trisomy
D056741:Cyclin D; D016213:Cyclins