原發性與轉移性胃癌同源關係和基因變化的特徵分析(1/2)
Date Issued
2002
Date
2002
Author(s)
吳明賢
DOI
902314B002167
Abstract
Gastrocarcinogenesis is consistent with the theory of invasive cancer
arising from a series of histological abnormalities in the multistep process
with accumulation of multiple alterations of critical growth-regulatory genes.
Although genetic changes associated with progression that may be used for
tumor characterization are beginning to be defined for GC, the range of
genetic abnormalities that are involved in metastases, their frequency of
occurrence, and their clinical and biological significance remain poorly
understcod. Furthermore, there have been no published data directly
comparing systemic genetic alterations in primary GC and their metastases.
The reasons why previous studies in this field were incomplete and lacking
are due to technical problems including inefficient microdissection and
incomprehensive investigations of whole genome. To overcome these
limitations, a comprehensive molecular cytogenetic technique called
comparative genomic hybridization (CGH) and a powerful microdissection
technique named laser capture microdissection (LCM) have recently been
developed. In the first year grant period, we have successfully established
the technique of CGH and utilized CGH to analyzed genetic alterations in 53
primary GC (figure 1). Our preliminary results have demonstrated
genomewide chromosomal alterations in primary GC and such genetic
profiles could provide a basis for further comparison with metastatic GC.
These findings also revealed histology and stage-related chromosomal
alterations. In addition, the application of LCM could precisely dissect
tumorous and nontumorous components from histologic sections (figure 2).
Since genomic DNA from LCM cells were not sufficient to perform CGH, we
used degenerate oligonucleotide primed-polymerase chain reaction
(DOP-PCR) to amplify DNA (figure 3). The amplified DNA then could be
subjected to CGH and the analyses were accurate to reflect the genetic
profiles of original cells.
With the aforementioned CGH, LCM, and DOP-PCR, we have
established an effective method to analyze genetic aberrations in primary
and metastatic GC. In the second year grant period, we will adopt these
methods to analyze genomewide alterations of primary and metastatic GC from different locations (e.g. lymph nodes, liver etc.)collected in the first year.
Such efforts might elucidate the clonal relationship between primary and
metastatic GC and disover useful predictive markers for GC.
Subjects
Gastric cancer
comparative genomic hybridization
laser capture
microdissection
microdissection
degenerative oligonucleotide primed-polymerase chain reaction
SDGs
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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