Analysis of genetic alterations associated with DNA diploidy, aneuploidy and multiploidy in gastric cancers.
OBJECTIVE
Recent studies have shown a close association between DNA ploidy status (diploidy, aneuploidy and multiploidy) identified by the crypt isolation technique and specific genetic alterations in colorectal carcinomas. However, such an association has not been elucidated for gastric tumors, even though they share common genetic features with colorectal carcinomas. In the present study, we established an association between DNA ploidy status and genetic alterations in gastric cancer.


METHODS
The DNA ploidy status of gastric tumors was classified as diploid, aneuploid or multiploid using the crypt isolation technique, which allows isolation of pure tumor crypt from tumor tissue. Crypt isolation combined with DNA cytometric sorting, polymerase chain reaction assay using 26 microsatellite markers and direct sequencing of the p53 gene were used to detect allelic imbalances [loss of heterozygosity (LOH) or allelic loss], microsatellite imbalance (MSI) and mutation of p53 in 54 gastric cancers (13 diploid, 12 aneuploid, 29 multiploid).


RESULTS
Diploid tumors showed few genetic alterations, including allelic imbalances and p53 mutations. In contrast, aneuploid tumors and multiploid tumors (in particular, aneuploid populations of multiploid tumors) exhibited multiple genetic alterations, including allelic imbalances and p53 mutations. In addition, the frequencies of genetic alterations observed in the corresponding diploid fractions of multiploid tumors were relatively higher than in diploid tumors. MSI was commonly observed in diploid, aneuploid and multiploid carcinomas.


CONCLUSIONS
The present results indicate that in gastric carcinomas, diploid tumors are generally non-LOH and MSI, whereas aneuploid and multiploid tumors are associated with LOH and MSI, suggesting that the genetic profile of these carcinomas is dependent on the tumor's ploidy status.
Sugai
Tamotsu
T
Division of Pathology, Central Clinical Laboratory, Iwate Medical University, Morioka, Japan. tsugai@cocoa.ocn.ne.jp
Habano
Wataru
W
Jiao
Yu-Fei
YF
Suzuki
Masamichi
M
Takagane
Akinori
A
Nakamura
Shin-Ichi
S
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002877:Chromosomes, Human / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D004171:Diploidy; D005260:Female; D005819:Genetic Markers; D042822:Genomic Instability; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011003:Ploidies; D016133:Polymerase Chain Reaction; D011123:Polyploidy; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D004273:DNA, Neoplasm; D005819:Genetic Markers; D016159:Tumor Suppressor Protein p53