Genetic alterations of the ATBF1 gene in gastric cancer.
OBJECTIVE
Alpha-fetoprotein (AFP)-producing gastric cancers are aggressive tumors with venous and lymphatic invasion and hepatic metastasis. The goal of the present study was to investigate whether somatic changes of the AFP-negative regulator AT motif binding factor-1 (ATBF1) gene are involved in the development or progression of gastric cancers and the production of AFP in gastric cancer cells.


METHODS
We searched for genetic alterations of the ATBF1 gene by single-strand conformational polymorphism and sequencing methods as well as allelic loss analysis with the microsatellite markers D16S3066 and D16S3139. Immunochemistry for AFP expression in gastric cancer cells was also done.


RESULTS
In 81 sporadic gastric cancers, four mutations were detected in seven cases: one was a missense mutation and three were deletions; loss of heterozygosity at the ATBF1 locus was detected in 52.9% of informative samples. Five of the eight cancers with AFP expression showed ATBF1 genetic alterations.


CONCLUSIONS
These results suggest that genetic alteration of the ATBF1 gene may contribute to the aggressive nature of gastric cancers and the production of AFP in gastric cancer cells.
Cho
Yong Gu
YG
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Song
Jae Hwi
JH
Kim
Chang Jae
CJ
Lee
Youn Soo
YS
Kim
Su Young
SY
Nam
Suk Woo
SW
Lee
Jung Young
JY
Park
Won Sang
WS
D000230:Adenocarcinoma / Q000235:genetics / Q000556:secondary; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D020125:Mutation, Missense; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C071660:ZFHX3 protein, human