IDENTIFICATION OF GENETIC ALTERATIONS ASSOCIATED WITH THE PROCESS OF HUMAN EXPERIMENTAL COLON-CANCER LIVER METASTASIS IN THE NUDE-MOUSE

Understanding the genetic elements controlling the process of tumor me tastasis to distant organ sites such as the liver may be the key to im proving survivorship from colon cancer, By using standard cytogenetic techniques in combination with comparative genomic hybridization, mult iple genetic imbalances within three human colon cancer cell lines pre viously selected for differences in liver-metastatic behavior were ide ntified, The entire genome of one poorly metastatic cell line (KM12C) was compared directly with that of two highly metastatic cell lines (K M12SM, KM12L4A) derived from it, A number of chromosomal gains (8q, 12 q15, 20q11.2) and losses (5p13, 6p21.3, 18) were common to all three c ell lines and are likely related to early tumor development rather tha n to the selection process used to generate cell lines of increased me tastatic potential, Chromosomal imbalances detected only in the highly metastatic cell lines were also observed, KM12SM showed losses of por tions of 2p22, 2q24.3-->2q32.2, 4p15.3-->cen, 4q24 without the 13q and 15q22.3 gains noted for KM12C. Both gains (1p31.3-->1p21, 2q22-->2q33 , 3cen-->3q26.2, 5q14-->5q23, 6cen-->6q23) and losses (16p, 17p, 17q, 19p, 19q, 22q) were observed for KM12L4A but not for the other two cel l lines, Identification of these alterations provides valuable insight into the process of experimental liver metastasis and is a first step towards mapping genes linked to the terminal phases of human colon ca ncer progression.