−8p12–23 and +20q Are Predictors of Subtypes and Metastatic Pathways in Colorectal Cancer: Construction of Tree Models Using Comparative Genomic Hybridization Data

Abstract

A substantial body of evidence suggests the genetic heterogeneous pattern and multiple pathways in colorectal cancer initiation and progression. In this study, we construct a branching tree and multiple distance-based tree models to elucidate these genetic patterns and pathways in colorectal cancer by using a data set comprised of 244 cases of comparative genomic hybridization. We identify the six most common gains of chromosomal regions of 7p (37.0%), 7q11-32 (34.8%), 8q (48.3%), 13q (49.1%), 20p (36.1%), and 20q (50.4%), and the nine most common losses of 1p13-36 (30.9%), 4p15 (24.3%), 4q33-34 (24.3%), 8p12-23 (50.9%), 15q13-14 (23.5%), 15q24-25 (24.3%), 17p (34.8%), 18p (36.5%), and 18q (61.7%) in colorectal cancer. We classify colorectal cancer into two distinct groups: one preceding with -8p12-23, and the other with +20q. The sample-based classification tree also demonstrates that colorectal cancer can be classified into multiple subtypes marked by -8p12-23 and +20q. By comparing chromosomal abnormalities between primary and metastatic colorectal cancer, we identify five potential metastatic pathways: (-18q, -18p), (-8p12-23, -4p15, -4q33-34), (+20q, +20p), (+20q, +7p, +7q11-32), and +8q. -8p12-23 and +20q are inferred to be the two marker events of colorectal cancer metastasis. The current oncogenetic tree models may contribute to our understanding towards molecular genetics in colorectal cancer. Particularly, the metastatic pathways we describe may provide pivotal clues for metastatic candidate genes, and thus impact on the prediction and intervention of metastatic colorectal cancer.