[Transforming growth factor beta receptor II mutations in RER positive colorectal cancers].
OBJECTIVE
To detect alterations of microsatellite loci [transforming growth factor beta receptor II (TGF-betaRII)(A)(10), TGF-betaRII(GT)(3), hMSH3(A)(8), hMSH6(C)(8), Bax(G)(8), IGFIIR(G)(8), IGFIIR(CT)(3)] and point mutations of TGF-betaRII (TGF-betaRII 452/454, TGF-betaRII 533).


METHODS
PCR-SSLP, microdissection-PCR-SSLP, PCR-SSCP, clone sequencing and immunohistochemistry were used.


RESULTS
The mutation rate of TGF-betaRII(A)(10) in RER+ (replication error positive) colorectal carcinomas was 33% (3/9). Similar mutations were also observed in adenomas with severe dysplasia. No mutations at other microsatellite loci were found. RER+ colorectal cancers mainly occurred in male patients at a young age and were more common in the colon than in the rectum (P < 0.05).


CONCLUSIONS
RER+ colorectal cancers were found in young males and commonly located in the colon. A one third mutation rate in TGF-betaRII(A)(10) in these patients is lower than that observed in western populations, which may imply diverse pathways of carcinogenesis of RER+ colorectal carcinoma. TGF-betaRII(A)(10) mutation may play a role in the transforming process from an adenoma with severe dysplasia to a full blown carcinoma.
Department of Pathology, School of Medicine, Zhejiang University, Hangzhou 310031, China. LMD@sun.zju.edu.cn
Mao-de
MD
Lai
Zhi-da
ZD
Huang
Qiong
Q
Huang
Jian
J
Chen
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D017354:Point Mutation; 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*
D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II