BMC Cancer 2007, 7:226 http://www.biomedcentral.com/1471-2407/7/226 Losses: 3p (84.1%), 4 (up to 74.1% on 4qter), 13q(14) (69.8%), 10(q) (41.3%), 17p13 (33.3%), 2(q23q24) (31.8%), 8p (25.4%), 9, 11, 15, 6q, 16q SCLC had the highest number of chromosomal imbal- ances (median 12 involved chromosomes per case). Also, some of the imbalances constituted the overall highest fractional aberrations in all datasets (e.g. >80% losses on 3p), as well as very frequent losses on 4q, 13q and 10q. Although frequent gains on 7p had been reported from array CGH of SCLC cell lines [74], this region was rarely involved in the mostly clinical specimen analyzed by chromosomal CGH. Endometrial carcinoma (56 cases) Gains: 1q (50%), 8q(22) (39.3%), 3q26 (14.3%), 10 (up to 14.3%) Losses: 10q (12.5%), 13q (10.7%), 14q, 9q As in e.g. nasopharynx ca., SCLC and pancreas ca., the maximum of 8q gains was proximal of 8q24. Endometrial ca. show an exceptional high rate of gains on 1q, which were also the most frequent change in a series of 98 cases not available for inclusion here [75]. Interestingly, chro- mosome 10 was also frequently involved (both gains and losses). Carcinomas of the vulva (53 cases) Gains: 3q (45.7%), 8q(23) (34%), 1 (up to 28.3%), 5p(15) (26.4%), 20q (24.5%), 9q (20.8%), 6, 7, 12, 14, 19, X Losses: 3p (22.6%), 4p (22.6%), 11q23q25 (20.8%), 13q14 (13.2%), 8p, 10, X Vulvar carcinomas showed an imbalance pattern charac- teristic for squamous cell neoplasias, with a high rate of gains on 8q23 and especially 3q. As in cervix ca., the most frequent changes could not be related to HPV status [76]. Squamous cell carcinomas of the skin (52 cases) Gains: 3q (11.5%), 17q (11.5%), Xq (9.6%), 1q, 8q, 14q Lossses: 9p21 (19.2%), 3p (13.5%), 18q (13.5%), 17p (9.6%) While containing many cases of borderline malignant behaviour, squamous skin neoplasias had the overall low- est aberration frequencies (median 0). This group did not include the pre-malignant keratoacanthomas, for which a frequent gain of 11q and cyclin D1 overexpression had been shown [77]. Disease-specific Involvement of most frequently aberrant chromosomes and relationship of overall aberration profiles Several chromosomal hot spot regions showed a pro- nounced disease related variation. The most prominent regions scoring high in specific entities are listed in Table 2. To reduce sampling bias (e.g. entity specific inclusion of a high proportion of early stage cases) top-scoring aberra- tions were defined as the most frequent gains or losses in each entity. Some additional imbalances which occured only in few entities at high levels are listed in Table 3. In an attempt to identify the relation of single case aberra- tion profiles, a cluster analysis of all 5043 informative cases was performed. For that purpose, a band specific matrix with 86 bands resolution was generated, of which the 55 intervals most frequently involved in imbalances were selected (top-scorers in one or more entities, ref. Tables 2 and 3; e.g. "8q2"). Hierarchical cluster analysis revealed the complexity of the case-specific aberration patterns, and was able to visualize concordance of imbal- ance patterns and disease categories in small groups of cases (Figure 3). To reduce the complexity of the data and simplify the detection of similarities in the aberration patterns of dif- ferent entities, region specific aberration frequencies of all entities were clustered. For each of the 55 selected inter- vals, the sum of gains – losses was calculated, resulting in a 22 × 55 matrix (entities × intervals). During hierarchical cluster analysis, values were normalized over each entity's intervals, to account for differences in genomic complex- ity. Figure 4 depicts the result of the cluster analysis, in which overall similarities and differences in the different entities become apparent. Differences in aberration profiles in some instances will reflect the general histological type, which is substantiated by the close relation of overall profiles e.g. from clinico- pathological groups containing squamous cell carcinoma cases (group NSCLC/esophagus/HNSCC/cervical/vulva in Figure 4). To evaluate this effect, the most frequent his- topathological entities (adenoca., squamous cell ca., hepatocellular ca., ductal breast ca., transitional cell ca., intestinal adenoca.) were selected. Additionally, adeno- carcinomas of the prostate were put in a separate group, due to the previous observation of specificities in the imbalance profile (e.g. overall lack of 1q gains). Cluster- ing was performed analogous to the method described above. Figure 5 visualizes the clustering of those his- topathological entities. In comparing the most frequent imbalances for their occurrence in different entities, some general observations stood out. Gains involving the terminal part of 8q were ubiquitously found, and often belonged to the most fre- Page 8 of 15 (page number not for citation purposes)