Transforming growth factor-beta receptor type 2 mutations and microsatellite instability in sporadic colorectal adenomas and carcinomas.
Frame-shift mutations in a run of 10 adenines (A10) of the transforming growth factor-beta receptor type 2 gene (TGF-beta RII) are commonly seen in inherited and sporadic colonic cancers that exhibit microsatellite instability. A10 mutations and instability also are commonly seen in hereditary nonpolyposis colon cancer-associated adenomas. However, instability is quite rare in sporadic adenomas, and the timing of acquisition of A10 mutations with respect to the sporadic adenoma-carcinoma sequence has not been reported. We evaluated 100 sporadic colorectal cancers and 164 sporadic adenomas for microsatellite instability with a set of 10 tetranucleotide polymerase chain reaction primer sets and for A10 frame-shift mutations. A10 mutations were significantly associated with microsatellite instability in colorectal cancers, being seen in 9 of 11 cancers with 50% or greater instability and in 0 of 89 tumors with less than 50% instability (P < 0.0001). A10 mutations were not detected in any adenomas, only three of which (1.8%) exhibited significant (30% or greater) instability. We conclude that both TGF-beta RII frame-shift mutations and microsatellite instability occur at a relatively late stage of sporadic colorectal tumorigenesis. A10 frame-shift mutations appear to be restricted to sporadic colorectal cancers with extensive microsatellite instability.
Samowitz
W S
WS
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
Slattery
M L
ML
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004276:DNA, Satellite / Q000032:analysis; D016368:Frameshift Mutation; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
D004276:DNA, Satellite; D018125:Receptors, Transforming Growth Factor beta