J Korean Med Sci.  2006 Aug;21(4):656-665. 10.3346/jkms.2006.21.4.656.

Genetic Alterations in Primary Gastric Carcinomas Correlated with Clinicopathological Variables by Array Comparative Genomic Hybridization

• Kang JU
• Kang JJ
• Kwon KC
• Park JW
• Jeong TE
• Noh SM
• Koo SH

• KMID: 2157817
• DOI: http://doi.org/10.3346/jkms.2006.21.4.656

Abstract

Genetic alterations have been recognized as an important event in the carcinogenesis of gastric cancer (GC). We conducted high resolution bacterial artificial chromosome array-comparative genomic hybridization, to elucidate in more detail the genomic alterations, and to establish a pattern of DNA copy number changes with distinct clinical variables in GC. Our results showed some correlations between novel amplified or deleted regions and clinical status. Copy-number gains were frequently detected at 1p, 5p, 7q, 8q, 11p, 16p, 20p and 20q, and losses at 1p, 2q, 4q, 5q, 7q, 9p, 14q, and 18q. Losses at 4q23, 9p23, 14q31.1, or 18q21.1 as well as a gain at 20q12 were correlated with tumor-node-metastasis tumor stage. Losses at 9p23 or 14q31.1 were associated with lymph node status. Metastasis was determined to be related to losses at 4q23 or 4q28.2, as well as losses at 4q15.2, 4q21.21, 4q 28.2, or 14q31.1, with differentiation. One of the notable aspects of this study was that the losses at 4q or 14q could be employed in the evaluation of the metastatic status of GC. Our results should provide a potential resource for the molecular cytogenetic events in GC, and should also provide clues in the hunt for genes associated with GC.

Keyword

Mutation; Genetic Alteration; Stomach Neoplasms; Chromosome-based comparative genomic hybridization; Gene Dosage; Copy-Number Gain; Copy-Number Loss

MeSH Terms

Stomach Neoplasms/genetics/*pathology
Reverse Transcriptase Polymerase Chain Reaction/methods
Receptors, Thyrotropin/genetics
Nucleic Acid Hybridization/*methods
Neoplasm Staging
Middle Aged
Male
MafB Transcription Factor/genetics
Lymphatic Metastasis/genetics
Humans
Genome, Human/genetics
Gene Expression Regulation, Neoplastic
Female
Chromosomes, Human, Pair 20/genetics
Chromosomes, Human, Pair 14/genetics
*Chromosome Aberrations
Aged, 80 and over
Aged
Adult

Figure

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  Fig. 1 Frequency of chromosomal copy number change in 28 gastroesophageal tumors. Gains and losses are shown as green and red bars, respectively, indicating the overall chromosomal copy number aberrations in the examined gastroesophageal tumors.

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  Fig. 2 Examples of microarray CGH results for four of the most frequently observed common regions. Whole genome profiles (A and D) are shown in the upper portion, and individual chromosome profiles (B, C, E and F) are shown in more detail below the profile of the entire genome. A representative chromosome profile, showing high-level amplifications from 3p14.2 (B) and 20q12 (C) in patient 18, and loss at 10q24.32 (E) and 14q31.1 (F) in patient 21.

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  Fig. 3 Relationship between TNM tumor stage and the clone mean number of chromosomal alterations (gains and losses). Tumor staging was determined on the basis of the UICC criteria.

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  Fig. 4 Comparison of array-CGH data with quantitative real-time RT-PCR of two selected genes in 28 gastroesophageal tumors. (A) MAFB gene expression at 20q12. (B) TSHR gene expression at 14q31.1. Patient numbers are listed on the x-axis. The values of expression for genes with no changes fall between 0.084 and 1.189. Gray columns represent the real-time RT-PCR results, whereas those in black represent the array-CGH results. con, control; TO1-TO28, Tumor 1-28.

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