Introduction 1 The cytogenetic profile of MDS In general, MDS show a characteristic genetic profile with an overweighing of unbalanced abnormalities. Most frequently, a loss of genetic material in the form of deletions and monosomies can be observed. A gain of genetic material with the appearance of total or partial trisomies is less frequent. Loss or gain of genetic material can also be the result of unbalanced translocations, which are frequently observed in MDS with multiple abnormalities. Taken together, it is thus obvious to assume that a prime molecular mechanism in MDS is the loss or inactivation of tumor suppressor genes, while the activation of oncogenes seems to be less relevant in myelodysplasia. 1 2 3 1 1 Table 1 Incidence of chromosome abnormalities in MDS related to 2,072 patients examined successfully Anomaly n n a n a n a 5q− 312 (15.1) 146 (47) 52 (17) 114 (36) −7/7q− 230 (11.1) 86 (37.5) 31 (13.5) 113 (49) +8 173 (8.4) 81 (46.8) 37 (21.4) 55 (31.8) −18/18q− 78 (3.8) 3 (3.8) 2 (2.6) 73 (93.6) 20q− 74 (3.6) 36 (48.6) 10 (13.5) 28 (37.8) −5 69 (3.3) 1 (1.4) 4 (5.8) 64 (92.8) −Y 58 (2.8) 41 (70.7) 5 (8.6) 12 (20.7) +21 45 (2.2) 5 (11.1) 18 (40) 22 (48.9) −17/17p− 42 (2.0) 1 (2.4) 1 (2.4) 40 (95.2) inv/t(3q) 41 (2.0) 16 (39) 8 (19.5) 17 (41.5) −13/13q− 40 (1.9) 5 (12.5) 6 (15) 29 (72.5) +1/+1q 37 (1.8) 3 (8.1) 6 (16.2) 28 (75.7) −21 33 (1.6) 3 (9.1) 4 (12.1) 26 (78.8) +11 28 (1.4) 6 (21.4) 4 (14.3) 18 (64.3) −12 26 (1.3) 0 2 (7.7) 24 (92.3) 12p− 25 (1.2) 7 (28) 6 (24) 12 (48) t(5q) 24 (1.2) 6 (25) 3 (12.5) 15 (62.5) 11q− 23 (1.1) 8 (34.8) 4 (17.4) 11 (47.8) 9q− 23 (1.1) 8 (34.8) 3 (13) 12 (52.2) t(7q) 22 (1.1) 6 (27.3) 6 (27.3) 10 (45.5) −20 22 (1.1) 0 0 22 (100) a Cytogenetic prognosis 4 7 8 9 10 2 2 3 1 Table 2 Cytogenetic prognostic findings in publications with greater than 100 patients examined Author, year Number of patients Abnormal (%) Favorable Intermediate Unfavorable Knapp 1985 174 66 (38) Normal (NN)  Complex Nowell 1986–1989 144 63 (44) 5q−, 20q− +8 −7/7q− Billström 1988 169 74 (44) NN, 5q− +8 −7/7q− Pierre 1989 247 106 (43) NN  Complex Morel 1993 408 151 (37) NN, 5q−, −Y, −7/7q−, 20q− +8 Complex Toyama 1993 401 200 (50) +8 −7/7q− Complex White 1994 198 75 (38) NN, 5q− 12p−, +21 Complex, +8, 20q− Greenberg 1997 816 327 (40) NN, 5q−, 20q−, −Y All others Complex, abnormal #7 Solé 2005 968 500 (51) NN, 5q−, 20q−, −Y, 11q−, 12p− rea 3q, + 8, +9, t11q, 17p− Complex, −7/7q−, i17q Haase 2007 2,072 1,080 (51) NN, +1/+1q, t(1q), 5q−, t(7q), 9q−, 12p−, abnormal #15, t(17q), 20q−, −21, + 21, −X, −Y rea 3q, −7, 7q−, +8, 11q−, t(11q23), +19, complex (=3) Complex (>3), t(5q) rea 1 3 10 11 Prognostic relevance of chromosome abnormalities 12 2 3 13 2 Good prognosis 4 3 1 Intermediate prognosis 2 3 14 10 15 Poor prognosis 16 1 3 5 7 2 15 10 3 Prognostic scoring 2 1 3 1 15 Fig. 1 p 15  Table 3 New cytogenetic prognostic subgroups of the German–Austrian MDS Study Group in 1,202 patients treated with supportive care only Cytogenetic risk Cytogenetic finding Number (%) Median survival (months) Good 12p− 7 (0.6) n.r. 9q− 6 (0.5) n.r. t(15q) 6 (0.5) n.r. 15q− 5 (0.4) n.r. +21 13 (1.1) 100.8 5q− 132 (11) 77.2 20q− 24 (2) 71.0 −X 6 (0.5) 56.4 normal karyotype 622 (51.7) 53.4 −Y 33 (2.8) 39.4 t(1q) 7 (0.6) 34.7 t(7q) 7 (0.6) 34.7 t(17q) 6 (0.5) 32.1 −21 6 (0.5) 32.0 Intermediate-I 11q− 11 (0.9) 26.1 +8 64 (5.3) 23.0 Intermediate-II t(11q23) 6 (0.5) 20.0 Any 3q abnormality 16 (1.3) 19.9 +19 5 (0.4) 19.8 7q− 11 (0.9) 19.0 Complex (=3 anomalies) 32 (2.7) 17.0 −7 42 (3.5) 14.0 Poor Complex (>3 anomalies) 134 (11.1) 8.7 t(5q) 7 (0.6) 4.4 n.r. 17 Delineation of the most relevant cytogenetic subgroups 5q−, monosomy 7, and complex abnormalities 5q deletions 1 2 3 18 21 22 23 1 24 2 1 Fig. 2 p p p p  4 Table 4 Frequencies (in percent of all cases with the respective primary abnormality) of accompanying abnormalities n n n Additional anomaly Percent Additional anomaly Percent Additional anomaly Percent +8 17 +21 10 5q− 23 +21 13 5q− 10 +21 11 −20/20q− 8 +8 10 der(3q21/q26) 7 −7 7 inv(3q) 5 +11 7 der/del(12p) 7 del(12p) 5 −7 5 der/del(3p) 5 t(11q23) 5 del(12p) 5 der/t(21q) 5 iso(17)(q10) 5 +13 5 t(11q23) 3 Others 50 +14 5 Others 35   +8* 5     del(1p) 5     Others 22 25 26 27 Monosomy 7 1 28 29 20 30 31 32 33 34 35 In extremely rare cases, for the so-called monosomy 7 syndromes, the abnormality has a familiar background. In a substantial portion of patients, a mutagen exposition (benzene, solvents, irradiation, or radio- and/or chemotherapy) was documented. 3 1 Fig. 3 p p p p  36 37 Complex abnormalities 38 1 3 39 40 39 41 39 42 39 43 44 45 46 47 48 Conclusions 49 1 50 52 53 54 53 54 New analytical tools like matrix CGH, microarray gene expression analyses, proteomics, and methylation profiling will add substantially to the understanding of pathogenesis, delineation of therapeutic targets, and individualization of therapy in MDS. Taken together cytogenetics is still the gold standard of genetic diagnosis in MDS providing “labels” like 5q−, monosomy 7, or complex abnormalities for disease entities with a common biological behavior and clinical as well as prognostic impact. In the future, scientific progress will depend on the ability to combine established and newly developed methods to gain a comprehensive understanding of MDS, which will translate into an individualized and highly effective and well-tolerable treatment for all patients with MDS.