Mutation of the transforming growth factor-beta type II receptor gene in right-sided colorectal cancer: relationship to clinicopathological features and genetic alterations.
The presence of inactivating mutations in the transforming growth factor-beta (TGF-beta) type II receptor (RII) gene in the colon cancer suggests that it may behave like a tumour suppressor gene. RII is mutated in the majority of colon tumours exhibiting widespread microsatellite instability, a characteristic generally referred to as the replication error phenotype (RER+). We investigated the association between RII mutations and various clinicopathological variables and genetic alterations in a large series of sporadic adenocarcinomas arising in the proximal colon. RII mutations were found in 17 per cent (36/210) of right-sided tumours and in 86 per cent (32/37) of those displaying RER+. They were associated with the absence of lymph node invasion (P = 0.04), poor histological differentiation (P = 0.006), and with a trend for improved patient survival. Tumours with an RII mutation also showed non-significant trends for a lower incidence of p53 protein overexpression and of p53, K-ras, and APC gene mutation compared with tumours with normal RII. These results indicate that right-sided colorectal tumours containing RII mutations resemble those with the RER+ phenotype in terms of their clinicopathological features and genetic alterations.
Department of Surgery, University of Western Australia, Nedlands, Australia. bjiac@cyllene.uwa.edu.au
B J
BJ
Iacopetta
J
J
Welch
R
R
Soong
A K
AK
House
X P
XP
Zhou
R
R
Hamelin
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D009363:Neoplasm Proteins; D018125:Receptors, Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53