A transforming growth factor beta 1 receptor type II mutation in ulcerative colitis-associated neoplasms.
OBJECTIVE
Numerous gastrointestinal tumors, notably sporadic and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias, gastric cancers, and esophageal carcinomas, manifest microsatellite instability. Recently, a transforming growth factor beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in colorectal carcinomas showing instability. One hundred thirty-eight human neoplasms (61 UC-associated, 35 gastric, 26 esophageal, and 16 sporadic colorectal) were evaluated for this TGF-beta 1RII mutation.


METHODS
Whether instability was present at other chromosomal loci in these lesions was determined. In lesions manifesting or lacking instability, the TGF-beta 1RII coding region polydeoxyadenine (poly A) microsatellite tract was polymerase chain reaction amplified with 32P-labeled deoxycytidine triphosphate. Polymerase chain reaction products were electrophoresed on denaturing gels and exposed to radiographic film.


RESULTS
Three of 18 UC specimens with instability at other chromosomal loci (17%) showed TGF-beta 1RII poly A tract mutation, including 2 cancers and 1 dysplasia; moreover, 2% of UC specimens without instability (1 of 43) (1 cancer), 81% of unstable sporadic colorectal cancers (13 of 16), and none of the 61 stable or unstable gastric or esophageal cancers contained TGF-beta 1RII mutations.


CONCLUSIONS
Mutational inactivation of the poly A microsatellite tract within TGF-beta 1RII occurs early and in a subset of unstable UC neoplasms and commonly in sporadic colorectal cancers but may be rare in unstable gastric and esophageal tumors.
Souza
R F
RF
Department of Medicine, University of Maryland School of Medicine, Baltimore, USA.
Lei
J
J
Yin
J
J
Appel
R
R
Zou
T T
TT
Zhou
X
X
Wang
S
S
Rhyu
M G
MG
Cymes
K
K
Chan
O
O
Park
W S
WS
Krasna
M J
MJ
Greenwald
B D
BD
Cottrell
J
J
Abraham
J M
JM
Simms
L
L
Leggett
B
B
Young
J
J
Harpaz
N
N
Meltzer
S J
SJ
D030201:Activin Receptors, Type I; D000230:Adenocarcinoma / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*
D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I