Transforming growth factor beta type II receptor gene mutations in adenomas from hereditary nonpolyposis colorectal cancer.
OBJECTIVE
Germline mutations of DNA mismatch repair genes are responsible for cancer susceptibility in hereditary nonpolyposis colorectal cancer (HNPCC) kindreds. Transforming growth factor beta type II receptor (TGF-beta RII) has been found to be somatically altered in HNPCC. The aim of this study was to clarify further the role of TGF-beta RII alterations in HNPCC tumorigenesis, particularly in adenomas.


METHODS
Fourteen adenoma specimens and 13 cancer specimens from 10 patients with HNPCC were screened for mutations in the short repeated sequences of the TGF-beta RII gene by polymerase chain reaction-single-strand conformation polymorphism. Mismatch repair genes, replication errors, and c-K-ras 2 were also analyzed in HNPCC tumors.


RESULTS
Alterations of the TGF-beta RII gene at the short poly(A) repeat were found in 8 (57%) adenoma specimens and 11 (85%) cancer specimens. They were found at an earlier stage of adenomas. Two adenoma specimens showed two-hit inactivation of mismatch repair genes. Replication errors were detectable in 13 (93%) adenoma specimens. Mutations in c-K-ras 2 codon 12 were detected at a 50% frequency in adenoma specimens.


CONCLUSIONS
These data indicate a strong association between TGF-beta RII gene alterations and adenoma-carcinoma progression in HNPCC.
Akiyama
Y
Y
Department of Hygiene and Oncology, School of Medicine, Tokyo Medical and Dental University, Japan.
Iwanaga
R
R
Saitoh
K
K
Shiba
K
K
Ushio
K
K
Ikeda
E
E
Iwama
T
T
Nomizu
T
T
Yuasa
Y
Y
D000328:Adult; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*
D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II