Chromosomal and microsatellite instability in sporadic gastric cancer.
BACKGROUND
Gastric cancer can progress through two pathways of genomic instability: chromosomal (CIN) and microsatellite instability (MSI). It is hypothesized that these two pathways are not always independent and that some tumors show overlap between these two mechanisms.


METHODS
A total of 98 sporadic gastric cancers were classified based on their MSI status, using microsatellite assay with BAT26. Evidence for CIN was investigated by identifying loss of heterozygosity (LOH) events on chromosome arms, 5q, 10p, 17p, 17q, and 18q, which are regions harboring tumor suppressor genes that are significant in gastric cancer development.


RESULTS
Twelve tumors (12%) showed high-frequency MSI (MSI-H). Overall, 43 of the tumors (44%) had at least one LOH event, with most frequent chromosomal losses observed on 10p and 18q (30%, respectively), followed by 5q (21%), 17p (14%), and 17q (12%). Interestingly, overlap was observed between CIN and MSI pathways. Of 43 cancers with LOH events, four (9%) were also MSI-H. It was also found that 48% of cancers without MSI-H had no LOH events identified, comprising a subgroup of tumors that were not representative of either of these two pathways of genomic instability.


CONCLUSIONS
These results suggest that molecular mechanisms of genomic instability are not necessarily independent and may not be fully defined by either the MSI or CIN pathways in sporadic gastric cancers.
Hiyama
Toru
T
Health Service Center, Hiroshima University, Higashihiroshima, Japan. tohiyama@hiroshima-u.ac.jp
Tanaka
Shinji
S
Yoshihara
Masaharu
M
Sasao
Shogo
S
Kose
Kazuhiro
K
Shima
Hideyuki
H
Tuncel
Handan
H
Ueno
Yoshitaka
Y
Ito
Masanori
M
Kitadai
Yasuhiko
Y
Yasui
Wataru
W
Haruma
Ken
K
Chayama
Kazuaki
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D042822:Genomic Instability; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology