Alterations of gene expression in human colorectal cancer. Biological implications
G. D. Steele Jr, S. Davis, H. Yow, J. M. Wong, E. N. Rivers, I. C. Summerhayes, T. S. Ravikumar and L. B. Chen
Department of Surgery, New England Deaconess Hospital, Boston, Mass.
Alterations in gene expression associated with colorectal cancer have been
difficult to study because mucosal cell progenitors are not available in
culture. We therefore examined specific genes in approximately 100 human
colon cancer cell lines using complementary DNA probes and found profound
alterations and heterogenity of gene expression in human colorectal
carcinoma. Our data imply that understanding human colorectal cancer will
not be accomplished by studying one or two oncogenes in a limited number of
cell lines or fresh human tissue. More appropriate postulates of
transformation to dictate experimental design may include the investigation
of proposed three-dimensional structural changes of interface chromatin or
other generalized structural relationships that could predispose to an
aberrant gene expression program during transformation. Furthermore,
focusing on mechanisms of initiation and defining the molecular genetic
markers of gastrointestinal mucosal initiation should lead to a more
focused set of genetic, rather than epigenetic, mechanisms that underlie
oncogenic transformation.
