[High-resolution analysis of chromosome 5 and identification of candidate genes in gastric cancer].
OBJECTIVE
To explore the relationship between loss of heterozygosity (LOH) of 5p with the histological phenotype in gastric cancer.


METHODS
Eighty pairs of tumor and adjacent normal mucosa samples were collected and genomic DNA was extracted. Total of 17 polymorphic microsatellite markers for 5p were used for LOH analysis. A part of samples were fixed in 10% buffered formalin and stained with H&E. Histological type of gastric cancer was defined according to Lauren's classification.


RESULTS
The average informative rate of all seventeen markers was 60.0%. The LOH at least in one locus was detected in 28 of the 80 (35.0%) cases. The highest LOH frequency occurring at D5S2849 (7.77 cM), with LOH frequency of 35.2% (19/54). The minimal LOH region was spanned from 6.67 to 9.41 cM (1.18 Mb, covering 2.7 cM), including D5S417, D5S2849, D5S1492 and D5S2088. In 28 with LOH, 24 (85.7%) cases were of intestinal type, and only 4 cases (14.3%) were of diffuse type. There is significant difference between LOH frequency in intestinal-type and diffuse-type gastric cancers (P < 0.01). Searching the NCBI database disclosed that this minimal deletion region at 5p15.33 covered 3 candidate genes, IRX1, IRX2, and CEI.


CONCLUSIONS
The molecular events in 5p 15.33 may be related with the morphological differentiation and development of gastric cancer. Gastric cancer with LOH of 5p15.33 locus tends to develop in to intestinal type. The cluster of candidate genes in 5p15.33 may be closely implicated in carcinogenesis of intestinal type gastric carcinoma.
Yu
Ying-yan
YY
Department of Surgery of Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China. yingyan3y@yahoo.com.cn
Ji
Jun
J
Lu
Yun
Y
Bu
Lei
L
Liu
Bing-ya
BY
Zhu
Zheng-gang
ZG
Lin
Yan-zhen
YZ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002895:Chromosomes, Human, Pair 5; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010641:Phenotype; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D018398:Homeodomain Proteins; C501591:IRX1 protein, human; C501595:IRX2 protein, human; D014157:Transcription Factors