Microsatellite instability and mutations of the transforming growth factor beta type II receptor gene in colorectal cancer.
The TGF beta type II receptor (RII) was found to be mutated within a polyadenine tract in 100 of 111 (90%) colorectal cancers with microsatellite instability. Other polyadenine tracts of similar length were mutated in these samples but not as frequently as RII. In most cases, the polyadenine tract mutations affected both alleles of RII, and in four tumors heterozygous for the polyadenine mutations, three had additional mutations that were expected to inactivate the other RII allele. These genetic data support the idea that RII behaves like a tumor suppressor during CR cancer development and is a critical target of inactivation in mismatch repair-deficient tumors.
Parsons
R
R
Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Myeroff
L L
LL
Liu
B
B
Willson
J K
JK
Markowitz
S D
SD
Kinzler
K W
KW
Vogelstein
B
B
D000818:Animals; D001483:Base Sequence; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D004276:DNA, Satellite / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004276:DNA, Satellite; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II