Biomedical subjects

Kwi Hye Koh

Publications and source records attributed to Kwi Hye Koh.

3 recordsLinked to original sources

PubMed2006

Differentially expressed proteins in gastrointestinal stromal tumors with KIT and PDGFRA mutations.

Most gastrointestinal stromal tumors (GIST) have activating mutations in either KIT or PDGFRA. However, a small subset of GIST lacks either mutation. To investigate the molecular characteristics of GIST according to mutation type, protein expression profiles in 12 GIST (2 cases with PDGFRA mutations, 8 cases with KIT mutations and 2 cases lacking either mutation) were analyzed using 2-DE and MALDI-TOF-MS. Comparative analysis of the respective spot patterns using 2-DE showed that 15 proteins were differently expressed according to the mutation status. Expression levels of septin and heat shock protein (HSP) 27 were increased in GIST with KIT mutations and annexin V was overexpressed in GIST lacking either mutation. Among the 15 proteins, overexpression of 5 proteins [annexin V, high mobility group protein 1 (HMGB1), C13orf2, glutamate dehydrogenase 1 and fibrinogen beta chain] and decreased expression of RoXaN correlated with a higher tumor grade. These findings suggest that differential protein expression can be used as a diagnostic biomarker. Moreover, it may play a role in the development and progression of GIST according to activating mutation type, as these proteins have been shown to be involved in tumor metastasis, apoptosis and immune response.

Electrophoresis, Gel, Two-Dimensional↗

PubMed2004

Different gene expression profiles between microsatellite instability-high and microsatellite stable colorectal carcinomas.

Recent molecular genetic studies have revealed that two major types of genomic instabilities, chromosomal instability (CIN) and microsatellite instability (MSI), exist in colorectal carcinomas. In order to clarify the molecular signature related to the CIN and MSI in colorectal carcinomas, we performed transcriptomic expression analysis on eight microsatellite instability-high (MSI-H) colorectal carcinomas and compared the results obtained with that of nine microsatellite stable (MSS) colorectal carcinomas using oligonucleotide microarrays containing 17 334 known genes and 1331 unknown genes or expression sequence tags (ESTs). Unsupervised two-way hierarchical clustering with 5724 genes successfully classified tumors from normal mucosa, and displayed a distinctive MSI-H carcinomas subgroup. Based on intensive filtering, 57 known genes and eight ESTs were found to be highly relevant to the differentiation of MSI-H and MSS colorectal carcinomas. These genes successfully distinguish the new test set of six MSI-H and five MSS colorectal carcinomas. Many up- and downregulated genes in MSI-H colorectal carcinomas were related to the previously reported phenotypic characteristics; increased mucin production and intense peritumoral immune response in MSI-H carcinomas. Some of these differences were confirmed by semiquantitative reverse transcription-PCR and immunohistochemical analysis. Our findings indicate that there are many different genetic and transcriptomic characteristics between MSI-H and MSS colorectal carcinomas, and some of these differently expressed genes can be used as diagnostic or prognostic markers.

Base Sequence↗

PubMed2003

Chromosomal imbalances in the colorectal carcinomas with microsatellite instability.

Recent molecular genetic studies have revealed that two major types of genomic instabilities, chromosomal instability and microsatellite instability, exist in the colorectal carcinomas. To clarify the relationship between chromosomal abnormalities and mismatch repair gene defects in colorectal carcinomas, we performed a chromosomal analysis on 39 colorectal carcinomas with high-microsatellite instability (MSI-H) and compared the results obtained with those of 20 right-sided microsatellite-stable (MSS) colorectal carcinomas. Chromosomal imbalances (CIs) in MSS colorectal carcinomas were more frequent than in MSI-H colon carcinomas by comparative genomic hybridization analysis (70% versus 31%, P = 0.004). The CI patterns of MSI-H and MSS carcinomas were different. Frequent CIs in MSI-H colon carcinomas were gains of 4q (15%) and 8q (8%), and losses of 9q (21%), 1p (18%), and 11q (18%). In contrast, frequent CIs in right-sided MSS colon carcinomas were gains of 8q (50%), 13q (35%), and 20q (25%), and losses of 18q (55%), 15q (35%), and 17p (30%). We compared the mutation status of 45 target genes and CIs in our MSI-H tumors. Among these 45 target genes, mutation of hRAD50, a member of the DNA repair genes, and FLJ11383 were significantly related to MSI-H colorectal carcinomas with CIs (P = 0.01 and P = 0.02, respectively). Our findings indicate that unique CIs were present in a subset of MSI-H colorectal carcinomas and that these CIs are related to the mutation of several target genes, especially of hRAD50.

Acid Anhydride Hydrolases↗