Genome-wide Search for Chromosomal Aberrations in Colorectal Cancer: Implications for Pathogenesis and Clinical Management

Abstract

SUMMARY
In the present review, we discuss the cytogenetic findings
we have made in karyotyping studies of colorectal cancer
examined during a 10-year-period at two Scandinavian institutions
(Lund University Hospital, Sweden and Odense
University Hospital, Denmark) as well as relevant findings
by comparative genome hybridization (CGH) since this
method too provides a global overview of genomic alterations.
Our total series consists of 280 cytogenetically investigated
colorectal tumors, of which 82 were benign lesions
(mostly adenomas), 162 were primary carcinomas,
and 36 were metastases. The cytogenetic studies of these
tumors enabled us to: 1. identify early, possibly initiating,
genetic events in colorectal tumorigenesis; 2. determine the
clonal relationship among synchronously growing, macroscopically
distinct colorectal adenomas as well as between
carcinomas and polyps growing in the same patients; and
3. describe the cytogenetic make-up of metastatic lesions
by comparing karyotypically primary tumors and their local
and distal metastases in individual patients. The correlation
of tumor karyotypes with clinicopathologic parameters
in the series, enabled us to demonstrate considerable
genetic heterogeneity in colorectal tumors with distinct cytogenetic
subgroups corresponding to at least two oncogenetic
pathways in sporadic large bowel cancer, as is known
to be the case also in hereditary colorectal tumors. Finally, the karyotypic pattern could provide valuable and in some
instances unique information about the prognosis of colorectal
cancer patients and, hence, clues as to how they
should best be treated.