Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers.
Chromosome deletions are the most common genetic events observed in cancer. These deletions are generally thought to reflect the existence of a tumour suppressor gene within the lost region. However, when the lost region does not precisely coincide with a hereditary cancer locus, identification of the putative tumour suppressor gene (target of the deletion) can be problematic. For example, previous studies have demonstrated that chromosome 18q is lost in over 60% of colorectal as well as in other cancers, but the lost region could not be precisely determined. Here we present a rigorous strategy for mapping and evaluating allelic deletions in sporadic tumours, and apply it to the evaluation of chromosome 18 in colorectal cancers. Using this approach, we define a minimally lost region (MLR) on chromosome 18q21, which contains at least two candidate tumour suppressor genes, DPC4 and DCC. The analysis further suggested genetic heterogeneity, with DPC4 the deletion target in up to a third of the cases and DCC or a neighbouring gene the target in the remaining tumours.
Thiagalingam
S
S
Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Lengauer
C
C
Leach
F S
FS
Schutte
M
M
Hahn
S A
SA
Overhauser
J
J
Willson
J K
JK
Markowitz
S
S
Hamilton
S R
SR
Kern
S E
SE
Kinzler
K W
KW
Vogelstein
B
B
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D015179:Colorectal Neoplasms / Q000235:genetics*; D000075389:DCC Receptor; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins / Q000235:genetics; D011956:Receptors, Cell Surface; D051901:Smad4 Protein; D015534:Trans-Activators; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D004268:DNA-Binding Proteins; C501910:Dcc protein, mouse; D005819:Genetic Markers; D011506:Proteins; D011956:Receptors, Cell Surface; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins