Trisomy Disorders

Trisomy 12

Posted on: October 30, 2008


Note trisomy 12 is the most common cytogenetic change in chronic lymphocytic leukemia (CLL); however, it has also been observed in other subtypes of B-cell lymphoproliferative disorders, where it is not seldomly a secondary change

Clinics and Pathology


B-cell chronic lymphocytic leukemia (B-CLL)

 Phenotype / cell stem origin

virgin CD5+ recirculating B-cell; the classical CLL phenotype is CD5+, CD23+, CD22-, CD79a-, FMC7-, sIg weak; trisomy 12 is more often observed in CLL with morphologically and immunologically atypical cells, displaying CD5 negativity or FMC7 positivity and strong surface immunoglobulin staining; trisomy 12 is present in proliferating cells and seems to be associated with the absence of mutation of the Ig variable region genes


trisomy 12 is found in one third of cytogenetically abnormal CLLs by conventional karyotype, and in about 12-54% of cases when interphase FISH is used


a significant difference comparing the therapy-free interval of patients with +12 and patients with other anomalies was found; this observation was repeatedly confirmed; however an adverse impact of +12 on survival could not be demonstrated until the IWCLL compiled karyotype and survival data from more than 400 patients and showed a median survival of 5.4 years versus 8.6 years versus 14 years in patients with +12 versus another single abnormality versus a normal karyotype, respectively; the preliminary results on a large series of patients analyzed by interphase FISH showed that +12 and 14q+ changes are associated with shorter survival times, compared to patients with 13q abnormalities and normal karyotypes; however prospective data are needed to further assess the prognostic value of this cytogenetic change


B-cell non Hogkin’s lymphomas, distinct from CLL, i.e.prolymphocyticleukemia, hairy cell leukemia, splenic lymphoma with villous lymphocytes (SLVL), Waldenström’s disease, follicular lymphoma, mantle cell lymphoma, and diffuse large cell lymphoma

Phenotype / cell stem origin

lack of specificity for a particular immunophenotype


no data are available concerning the prognostic significance of +12, except in one series of mantle cell lymphomas in which it was the only single cytogenetic parameter associated with poor prognosis


Cytogenetics Morphological

using restriction fragment length polymorphism analysis, the extra chromosome 12 has been shown to derive from duplication of one chromosome 12, with retention of the other homolog rather than from triplication of one homolog; trisomy 12 is thought to be a secondary change since combined immunological and cytogenetic studies showed that it is present in only a part of the neoplastic B-cells; cases with partial duplication 12q were analyzed by FISH, and a “minimal duplicated region” could be defined in segment 12q13-12q15

External Links

Other database +12 or trisomy 12 Mitelman database (CGAP – NCBI)


Clinical significance of cytogenetic findings in untreated patients with B-cell chronic lymphocytic leukemia. Sadamori N, Han T, Minowada J, Sandberg AA. Cancer Genet Cytogenet 1984; 11: 45-51. Medline 6606486   Origin of trisomy 12 in B-cell chronic lymphocytic leukemia. Crossen PE, Horn HL. Cancer Genet Cytogenet 1987; 28: 185-186. Medline 3475165   Consistency of chromosomal aberrations in chronic B-lymphocytic leukemia. Juliusson GK, Friberg K, Gahrton G. Cancer 1988; 62: 500-506. Medline 3260535   Molecular analyses of chromosome 12 in chronic lymphocytic leukemia. Einhorn S, Burvall K, Juliusson G, Garhton G, Meeker T. Leukemia 1989; 3: 871-874. Medline 2586180   Prognostic subgroups in B-cell chronic lymphocytic leukemia defined by specific chromosomal abnormalities. Juliusson G, Oscier DG, Fitchett M, Ross FM, Stockdill G, Mackie MJ, Parker AC, Castoldi GL, Cuneo A, Knuutila S, Elonen E, Gahrton G. N Engl J Med 1990; 323: 720-724. Medline 2201915   Cytogenetic findings and survival in B-cell chronic lymphocytic leukemia. Juliusson G, Oscier D, Gahrton G. Leukemia Lymphoma 1991; Suppl: 21-25.   Trisomy 12 in chronic lymphocytic leukemia detected by fluorescence in situ hybridization : Analysis by stage, immunophenotype, and morphology. Que TH, Garcia-Marco J, Ellis J, Matutes E, Brito-Babapulle V, Boyle S, Catovsky D. Blood 1993; 82: 571-575. Medline 7687164   Trisomy 12 is uncommon in typical chronic lymphocytic leukaemias. Criel A, Wlodarska I, Meeus P, Stul M, Louwagie A, Van Hoof A, Hidajat M, Mecucci C, Van den Berghe H. Br J Haematol 1994; 87: 523-528. Medline 7993792   Correlation of trisomy 12 with expression of the proliferating nuclear antigen K-67 in chronic lymphocytic leukemia. Garcia-Marco J, Matutues E, Price CM, Ellis J, Que TH, Lens D, Catovsky D. Br J Haematol 1994; 86 (Suppl 1): 24.   Trisomy 12 in B-cell chronic lymphocytic leukaemia : assessment of lineage restriction by simultaneous analysis of immunophenotype and genotype in interphase cells by fluorescence in situ hybridization. Garcia-Marco J, Matutes E, Morilla R, Ellis J, Oscier D, Fantes J, Catovsky D, Price CM. Br J Haematol 1994; 87: 44-50.   Cytogenetic analysis of B cell chronic lymphoid leukemias classified according to morphologic and immunophenotypic (FAB) criteria. Hernandez JM, Mecucci C, Criel A, Meeus P, Michaux L, Van Hoof A, Verhoef G, Louwagie A, Scheiff J-M, Michaux J-L, Boogaerts M, Van den Berghe H. Leukemia 1995; 9: 2140-2146. Medline 8609731   Trisomy 12 defines a group of CLL with atypical morphology : correlation between cytogenetic, clinical and laboratory features in 544 patients. Matutes E, Oscier D, Garcia-Marco J, Ellis J, Copplestone A, Gillingham R, Hamblin T, Lens D, Swansbury GJ, Catovsky D. Br J Haematol 1996; 92: 382-388. Medline 8603004   Genetic abnormalities in chronic lymphocytic leukemia and their clinical and prognostic implications. Dierlamm J, Michaux L, Criel A, Wlodarska I, Van Den Berghe H, Hossfeld DK. Cancer Genet Cytogenet 1997; 94: 27-35. Medline 9078288   FISH Identifies different types of duplications with 12q13-15 as the commonly involvedsegment in B-cell lymphoproliferative malignancies characterized by partial trisomy 12. Dierlamm J, Wlodarska I, Michaux L, Vermessch JR, Meeus P, Stul M, Criel A, Verhoed G, Thomas J, Delannoy A, Louwagie A, Cassiman J.J., Mecucci C, Hagemeijer A, Van den Berghe H. Genes, Chromosom, Cancer 1997; 20: 155-166. Medline 9331566   Catalogue of chromosome aberrations in cancer. Mitelman F, Johansson B, Mertens F. Wiley-Liss Ed., Ney York,CD-ROM 1998.   Cytogenetic profile of lymphoma of follicle mantle lineage: correlation with clinicobiologic features. Cuneo A, Bigoni R, Rigolin GM, Roberti MG, Bardi A, Piva N, Milani R, Bullrich F, Veronese ML, Croce C, Birg F, Dohner H, Hagemeijer A, Castoldi GL. Blood 1999; 93: 1372-1380. Medline 9949181   Chromosome aberrations in B-cell chronic lymphocytic leukemia : reassessment based on molecular cytogenetic analysis. Dohner H, Stilgenbauer S, Dohner K, Bentz M, Lichter P. J Mol Med 1999; 77: 266-281. Medline 10023780   Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Hamblin TJ, Davis Z, Gardiner A, Ascier DG, Stevenson FK. Blood 1999; 94: 1848-1854. Medline 10023780


Written 05-2000 Lucienne Michaux




Trisomy 12 Mosaicism

Detection of trisomy 12 by fluorescent in situ hybridization (FISH) in cronic lymphocytic leukemia

Trisomy 12 mosaicism in a 7 year old girl with dysmorphic features and normal mental development

Trisomy 12 in Ewing’s Sarcoma

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