[Promoter hypermethylation and loss of heterozygosity of the APC gene in patients with familial adenomatous polyposis].
OBJECTIVE
To investigate the status of hypermethylation in the promoter 1A region of the adenomatus polyposis coli (APC) gene in 3 familial adenomatous polyposis (FAP) pedigrees and to screen large fragment deletions in the APC gene.


METHODS
DNA from tumor tissues and corresponding normal tissues of 5 FAP patients was modified by sodium bisulfite. Then the methylation status of the APC gene was analyzed by methylation specific-PCR (MSP) and DNA sequencing. Multiplex ligation-dependent probe amplification (MLPA) was used to screen aberrations involving large fragments from all the 15 exons and promoter region of APC gene.


RESULTS
No methylation was present in normal tissues. Hypermethylation was found in tumor tissues of one proband and her son. Loss of heterozygosity was observed in another patient from the same FAP family.


CONCLUSIONS
Aberrant methylation of the APC promoter region provides an important mechanism for impairing APC function and may occur early during colon neoplasia progression. Loss of heterozygosity may play a role in patients with classical polyposis.
Zhang
Yuan-ying
YY
Department of Genetics and Molecular Biology, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, 210009 People's Republic of China. Yuanying_z@163.com
Chen
Sen-qing
SQ
Zhu
Ming
M
Li
Jin-tian
JT
Ma
Guo-jian
GJ
Zhang
Xiao-mei
XM
Zhou
Jian-nong
JN
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000328:Adult; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000502:physiology*
D025601:Adenomatous Polyposis Coli Protein; D004273:DNA, Neoplasm