Construction and analysis of tree models for chromosomal classification of diffuse large B-cell lymphomas.
ABSTRACT To construct tree models for classification of diffuse large B-cell lymphomas (DLBCL) by chromosome copy numbers, to compare them with cDNA microarray classification, and to explore models of multi-gene, multi-step and multi-pathway processes of DLBCL tumorigenesis.
Maximum-weight branching and distance-based models were constructed based on the comparative genomic hybridization (CGH) data of 123 DLBCL samples using the established methods and software of Desper et al. A maximum likelihood tree model was also used to analyze the data. By comparing with the results reported in literature, values of tree models in the classification of DLBCL were elucidated.
Both the branching and the distance-based trees classified DLBCL into three groups. We combined the classification methods of the two models and classified DLBCL into three categories according to their characteristics. The first group was marked by +Xq, +Xp, -17p and +13q; the second group by +3q, +18q and +18p; and the third group was marked by -6q and +6p. This chromosomal classification was consistent with cDNA classification. It indicated that -6q and +3q were two main events in the tumorigenesis of lymphoma.
Tree models of lymphoma established from CGH data can be used in the classification of DLBCL. These models can suggest multi-gene, multi-step and multi-pathway processes of tumorigenesis. Two pathways, -6q preceding +6q and +3q preceding +18q, may be important in understanding tumorigenesis of DLBCL. The pathway, -6q preceding +6q, may have a close relationship with the tumorigenesis of non-GCB DLBCL.
- SourceAvailable from: Alejandro A Schaffer[show abstract] [hide abstract]
ABSTRACT: Oral cancer develops and progresses by accumulation of genetic alterations. The interrelationship between these alterations and their sequence of occurrence in oral cancers has not been thoroughly understood. In the present study, we applied oncogenetic tree models to comparative genomic hybridization (CGH) data of 97 primary oral cancers to identify pathways of progression. CGH revealed the most frequent gains on chromosomes 8q (72.4%) and 9q (41.2%) and frequent losses on 3p (49.5%) and 8p (47.5%). Both mixture and distance-based tree models suggested multiple progression pathways and identified +8q as an early event. The mixture model suggested two independent pathways namely a major pathway with -8p and a less frequent pathway with +9q. The distance-based tree identified three progression pathways, one characterized by -8p, another by -3p and the third by alterations +11q and +7p. Differences were observed in cytogenetic pathways of node-positive and node-negative oral cancers. Node-positive cancers were characterized by more non-random aberrations (n = 11) and progressed via -8p or -3p. On the other hand, node-negative cancers involved fewer non-random alterations (n = 6) and progressed along -3p. In summary, the tree models for oral cancers provided novel information about the interactions between genetic alterations and predicted their probable order of occurrence.International Journal of Cancer 02/2009; 124(12):2864-71. · 6.20 Impact Factor