Genetic alterations of the KLF6 gene in gastric cancer.
The KLF6 is a zinc-finger tumor suppressor that is frequently mutated in several human cancers and broadly involved in differentiation and development, growth-related signal transduction, cell proliferation, apoptosis, and angiogenesis. To determine whether genetic alterations of KLF6 gene are involved in the development and/or progression of gastric cancer, we have screened a set of 80 sporadic gastric cancers for mutations and allele loss of the KLF6 gene. Four missense mutations, S155R, P172 T, S180L, and R198 K, were detected in transactivation domain of the KLF6 gene and one of them had biallelic mutations with somatic mutation of one allele and loss of the remaining allele. All of the cases with mutation were of advanced intestinal-type gastric cancer with lymph node metastasis. In addition, 16 (43.2%) of 37 informative cases showed allelic loss at KLF6 locus. Interestingly, allelic loss was also frequent in intestinal-type gastric cancer. Therefore, our data suggest that genetic alterations of KLF6 gene might play an important role in the development or progression of sporadic gastric cancers.
Cho
Yong Gu
YG
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.
Kim
Chang Jae
CJ
Park
Cho Hyun
CH
Yang
Young Mok
YM
Kim
Su Young
SY
Nam
Suk Woo
SW
Lee
Sug Hyung
SH
Yoo
Nam Jin
NJ
Lee
Jung Young
JY
Park
Won Sang
WS
D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D019656:Loss of Heterozygosity; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators