Please use this identifier to cite or link to this item:
Title: A study of genomic aberrations in gastric adenocarcinoma
Keywords: Stomach, Gastric, Cancer, Genome, CGH, Array
Issue Date: 24-Jul-2009
Citation: ALVIN ENG KIM HOCK (2009-07-24). A study of genomic aberrations in gastric adenocarcinoma. ScholarBank@NUS Repository.
Abstract: Despite declining incidence and mortality, gastric cancer remains the fourth most common cancer and the second leading cause of death in the world. Gastric carcinogenesis is believed to occur through one of 3 pathways, the commonest of which involves sequential changes in mucosal histology, from normal through intestinal metaplasia and dysplasia to overt carcinoma. We aimed to investigate the genomic changes that parallel these mucosal transformations as they progress along the pathway described by Correa in 1988. 57 specimens representing the histological types of overt carcinoma, dysplasia, intestinal metaplasia and adjacent histologically normal mucosa were obtained from the archived formalin-fixed paraffin-embedded pathology blocks of 17 patients. Genomic DNA was extracted from each specimen. Comparative genomic hybridization was performed using a validated 2464-BAC clone array having an average inter-clone interval of 1.4 Mb. Our results revealed that all 4 histological types harbored extensive genomic changes that were highly similar. Further array CGH experiments conducted with tissue harvested from non-cancer gastrectomy specimens showed no evidence of significant copy number aberrations. Additional experiments found that the distant margin blocks of the same cancer patients had a distinctly different genomic signature compared to the earlier 57 specimens. Several prospective sets of specimens that were harvested and processed in our laboratory confirmed that the genomic profile of gastric mucosa at the margin of a cancer resection is almost normal while the copy number aberrations in adjacent histologically normal gastric mucosa mirror those found in the tumor itself. Several regions of interest that were found in our study included the +20q13, +8z23, -19p13 and +17q21 cytobands. These copy number aberrations were present in the adjacent mucosa as well as in the tumors. The genome-wide study of adjacent normal mucosa in gastric cancer with arrayCGH has not been reported before and our findings are consistent with and provide genomic evidence for field cancerization in gastric adenocarcinoma. Our findings in gastric carcinoma are supported by recent discoveries of genomic, proteomic and nanoscale structural abnormalities in histologically normal adjacent colonic, prostatic, pancreatic and pulmonary tissue from cancer patients. The concept of field cancerization was first proposed in 1953. This theory suggests that chronic exposure to a DNA-damaging agent such as a chemical compound or an infection like H.pylori leads to the clonal expansion of inappropriate cell types that exhibit genetic instability. This premalignant state would eventually lead to transformation into overt carcinoma. The field cancerization theory mirrors the Correa hypothesis and it provides some explanation for the frequency of recurrence in gastric cancer patients. The understanding of gastric carcinogenesis as a field cancerization event would provide the impetus to focus resources on the study of premalignant histologically normal gastric mucosa that harbors the initiators of gastric carcinogenesis.
Appears in Collections:Master's Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
MSc thesis_Genomic Aberrations in Gastric Adenocarcinoma.pdf10.24 MBAdobe PDF



Google ScholarTM


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.