Involvement of Kruppel-like factor 6 (KLF6) mutation in the development of nonpolypoid colorectal carcinoma.
OBJECTIVE
To examine Kruppel-like factor 6 (KLF6) mutations in nonpolypoid-type tumors and alterations of K-ras, p53, and B-raf in relation between mutation and morphologic type, particularly nonpolypoid-type colorectal carcinomas.


METHODS
Fifty-five early nonpolypoid colorectal carcinomas were analyzed. Loss of heterozygosity (LOH) of KLF6 and p53 was determined by microsatellite assay. Mutations of KLF6, K-ras, and B-raf were examined by polymerase chain reaction-single-strand conformation polymorphism followed by direct sequencing. In LOH-positive and/or mutation-positive tumors, multiple (4-7) samples in each tumor were microdissected and examined for genetic alterations. p53 expression was evaluated by immunohistochemistry.


RESULTS
LOH of KLF6 and p53 was found in 14 of 29 (48.3%) and 14 of 31 (45.2%) tumors, respectively. In 10 of the 14 (71.4%) KLF6 LOH-positive tumors and 9 of the 14 (64.3%) p53 LOH-positive tumors, LOH was found in all of the microdissected samples. In 1 of the 10 (10.0%) KLF6 LOH-positive tumors, a single missense mutation was identified. K-ras and B-raf mutations were found in 5 of 55 (9.1%) and 6 of 55 (10.9%) tumors, respectively. However, these mutations were detected only in subsets of microdissected tumor samples.


CONCLUSIONS
These data suggest that KLF6 and p53 mutations are involved in the development of nonpolypoid colorectal carcinoma, whereas K-ras and B-raf mutations are not.
Department of Endoscopy, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Shinichi
S
Mukai
Toru
T
Hiyama
Shinji
S
Tanaka
Masaharu
M
Yoshihara
Koji
K
Arihiro
Kazuaki
K
Chayama
D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000502:physiology; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf