DNA copy number changes in young gastric cancer patients with special reference to chromosome 19

Abstract

Only a few cytogenetic and genetic studies have been performed in gastric cancer patients in young age groups. In the present study we used the comparative genomic hybridisation (CGH) method to characterise frequent DNA copy number changes in 22 gastric cancer patients of 45 years or younger and three gastric cancer cell lines established from patients younger than 45 years. Analysis of DNA copy number changes revealed frequent DNA copy number increases at chromosomes 17q (52%), 19q (68%) and 20q (64%). To confirm the CGH results and to characterise the amplicon region on the most frequently amplified chromosome, chromosome 19, we carried out fluorescence in situ hybridisation (FISH) analysis and Southern blot analysis. Fluorescence in situ hybridisation with the bacterial artificial chromosome (BAC) clone mapped to 19q12 indicated a copy number increase in all eight tumour specimens studied. Southern blot analysis of six tumour specimens and three tumour cell lines, with five probes mapped to the 19q12 -13.2 region, suggested cyclin E to be one of the candidate target genes in the 19q region for gastric cancer tumorigenesis. Cyclin E protein overexpression was verified in tumours with amplification on chromosome 19. Further studies are required to investigate the biological and clinical significance of 19q amplicon and cyclin E upregulation in gastric cancer of young patients. British Journal of Cancer (2003Cancer ( ) 88, 1914Cancer ( -1919Cancer ( . doi:10.1038 (Parkin et al, 1999), but in young age groups it is rather uncommon. Several studies have been published about gastric cancer in young patients aged 45 years or younger (Kokkola et al,

Exclusion of RUNX3 as a tumour-suppressor gene in early-onset gastric carcinomas

“…Noteworthy, a previous study using CGH showed gains in the short arm of chromosome 1 in this case (Varis et al, 2003). Chromosome 1 aberrations were also observed in LOH cases.…”

Genetic alterations in 102 primary gastric cancers by comparative genomic hybridization: gain of 20q and loss of 18q are associated with tumor progression

“…Previous CGH studies of gastric cancers yielded similar results. Moreover, several CGH studies identified the 20q region as the most frequent site of gain of DNA in gastric [29][30][31][32]34,35,39 Amplification at 20q has been reported in several cancers, such as colon cancer, 40 pancreatic cancer, 41,42 lung adenocarcinoma, 43 ovarian carcinoma, 44 and osteosarcoma. 45 In our study, gain of 20q was detected in 71 cases (70%) and was associated with the pattern of the cancer-stroma 51 and CYP24 (20q13.2).…”

“…In several studies, frequent chromosomal alterations, namely, gains on 1p, 6p, 7q, 8q, 11q, 16p, 17q, 20q, and 22q, and deletions on 3p, 4q, 5q, 9p, 16q, 17p, 18q, and 19p were observed in gastric cancer. [28][29][30][31][32][33][34][35] Recently, microarray technologies have emerged as key tools for the expression analysis of gene and genes expressed in gastric cancers have been examined using cDNA microarray technique. 36 In the present study, to identify regions of the genome that might be involved in the oncogenesis of gastric cancers, we made an extensive study of chromosomal alterations in such cancers by CGH.…”

Genetic Instability in Gastric Cancer

“…They concluded that these differences in genomic profiles likely reflect different pathogenic mechanisms of the disease. Varis et al, similarly observed that the most frequent cytogenetic aberrations were gains seen at 17q, 19q, and 20q in younger patients (Varis et al, 2003). They also found that DNA copy number changes were mostly detected in intestinal or mixed types of tumours.…”