Apparent protection from instability of repeat sequences in cancer-related genes in replication error positive gastrointestinal cancers.
Genomic instability at simple repeated sequences has been observed in various types of human cancers and is considered an important mechanism in tumorigenesis. Alterations at microsatellite loci have been reported scattered throughout the genome. Recently, the transforming growth factor-beta receptor type II (TGF-beta RII) and the insulin-like growth factor II receptor (IGF-IIR) genes were shown to have inactivating mutations within coding microsatellite sequences. The demonstration of mutations in two growth regulatory genes supports the idea that other regulatory genes with repeat sequences may also be targets in tumours with defective mismatch repair. We examined genes involved in tumour suppression, cell adhesion and cell cycle regulation for mutations at small repeat sequences in replication error positive gastrointestinal cancers. Several polymorphisms were found which exhibited instability, but no other instability was present in the regions examined.
Simms
L A
LA
Glaxo Conjoint Gastroenterology Laboratory, Royal Brisbane Hospital Foundation Clinical Research Centre, Australia.
Zou
T T
TT
Young
J
J
Shi
Y Q
YQ
Lei
J
J
Appel
R
R
Rhyu
M G
MG
Sugimura
H
H
Chenevix-Trench
G
G
Souza
R F
RF
Meltzer
S J
SJ
Leggett
B A
BA
D030201:Activin Receptors, Type I; D000230:Adenocarcinoma / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008025:Ligases; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011506:Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D011960:Receptors, Estrogen / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D013274:Stomach Neoplasms / Q000235:genetics*; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D051176:beta Catenin
C493956:CDKN1A protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C000607071:RARA protein, human; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D018125:Receptors, Transforming Growth Factor beta; D000072482:Retinoic Acid Receptor alpha; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D008025:Ligases; C497446:VHL protein, human