• Proceedings of the Korean Society for Bioinformatics Conference
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• 2000.11a
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• pp.74-82
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• 2000

Prostate cancer initially responds and regresses in response to androgen depletion therapy, but most human prostate cancers will eventually recur, and re-grow as an androgen independent tumor. Once these tumors become hormone refractory, they usually are incurable leading to death for the patient. Little is known about the molecular details of how prostate cancer cells regress following androgen ablation and which genes are involved in the androgen independent growth following the development of resistance to therapy. Such knowledge would reveal putative drug targets useful in the rational therapeutic design to prevent therapy resistance and control androgen independent growth. The application of genome scale technologies have permitted new insights into the molecular mechanisms associated with these processes. Specifically, we have applied functional genomics using high density cDNA microarray analysis for parallel gene expression analysis of prostate cancer in an experimental xenograft system during androgen withdrawal therapy, and following therapy resistance, The large amount of expression data generated posed a formidable bioinformatics challenge. A novel template based gene clustering algorithm was developed and applied to the data to discover the genes that respond to androgen ablation. The data show restoration of expression of androgen dependent genes in the recurrent tumors and other signaling genes. Together, the discovered genes appear to be involved in prostate cancer cell growth and therapy resistance in this system. We have also developed and applied tissue microarray (TMA) technology for high throughput molecular analysis of hundreds to thousands of clinical specimens simultaneously. TMA analysis was used for rapid clinical translation of candidate genes discovered by cDNA microarray analysis to determine their clinical utility as diagnostic, prognostic, and therapeutic targets. Finally, we have developed a bioinformatic approach to combine pharmacogenomic data on the efficacy and specificity of various drugs to target the discovered prostate cancer growth associated candidate genes in an attempt to improve current therapeutics.

• Genomics & Informatics
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• v.2 no.3
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• pp.113-120
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• 2004

• Journal of Genetic Medicine
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• v.4 no.1
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• pp.15-21
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• 2007

Hereditary syndromes cause approximately 5 to 10% of overall cancer cases. Cancer related with genetic syndromes are found elsewhere, including stomach, breast, colorectum, ovary, brain and so on. Because hereditary cancers are due to germline mutations, these patients have unique clinical features distinct from sporadic cancer. Generally these features include (i) early age-of onset of cancer, (ii) frequent association with synchronous or metachronous tumors, (iii) frequent bilateral involvement in paired organs (iv) frequent association with other site tumors or characteristic clinical manifestation specific to each genetic syndrome. Due to these differences, the management strategy for patients with hereditary cancer is quite different from that for sporadic cancer. Additionally, there are important screening and surveillance implications for family members. Genetic counselling is prerequisite to these families for risk assessment by pedigree analysis, and guidance to clinical or genetic testing. The genes responsible for these syndromes has recently identified, as a result, genetic testing has become important determining factor in clinical decisions.

• Genomics & Informatics
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• v.21 no.1
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• pp.11.1-11.5
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• 2023

Breast cancer is the most common cancer worldwide, and advanced breast cancer with metastases is incurable mainly with currently available therapies. Therefore, it is essential to understand molecular characteristics during the progression of breast carcinogenesis. Here, we report a dataset of whole genomes from the human mammary epithelial cell system derived from a reduction mammoplasty specimen. This system comprises pre-stasis 184D cells, considered normal, and seven cell lines along cancer progression series that are immortalized or additionally acquired anchorage-independent growth. Our analysis of the whole-genome sequencing (WGS) data indicates that those seven cancer progression series cells have somatic mutations whose number ranges from 8,393 to 39,564 (with an average of 30,591) compared to 184D cells. These WGS data and our mutation analysis will provide helpful information to identify driver mutations and elucidate molecular mechanisms for breast carcinogenesis.

• Journal of Breast Cancer
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• v.21 no.4
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• pp.382-390
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• 2018

Purpose: PIK3CA mutation is considered to be a possible cause for resistance to neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the association between PIK3CA mutations and the outcome of NAC in HER2-positive breast cancers. Methods: A total of 100 HER2-positive breast cancer patients who had undergone NAC and surgery between 2004 and 2016 were examined. Mutation status was sequentially assessed in pre-NAC, post-NAC, and recurrent specimens taken from these patients. Results: PIK3CA mutations were identified in the sequential specimens of 17 patients (17.0%). These 17 patients experienced shorter disease-free survival (DFS) than the rest of the patients (58.3 months vs. 119.3 months, p=0.020); however, there was no significant difference in pathologic complete response (pCR) and overall survival (OS) (pCR, 17.6% vs. 33.7%, p=0.191; OS, 84.5 months vs. 118.0 months, p=0.984). While there was no difference in pCR between the wild-type and mutant PIK3CA groups in pre-NAC specimens (25.0% vs. 31.8%, p=0.199), PIK3CA mutations correlated with lower pCR in postNAC specimens (0.0% vs. 24.3%, p<0.001). Multivariate analysis revealed significantly worse DFS in the mutant PIK3CA group than in the wild-type group (hazard ratio, 3.540; 95% confidence interval, 1.001-12.589; p=0.050). Moreover, the DFS curves of the change of PIK3CA mutation status in sequential specimens were significantly different (p=0.016). Conclusion: PIK3CA mutation in HER2-positive breast cancer was correlated with a lower pCR rate and shorter DFS. These results suggest that PIK3CA mutation is a prognostic marker for NAC in HER2-positive breast cancer, especially in post-NAC specimens.

• Journal of Gastric Cancer
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• v.23 no.1
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• pp.107-145
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• 2023

The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8041-8045
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• 2016

Cervical cancer is one of the most common cancers in women worldwide. During their life time the vast majority of women become infected with human papillomavirus (HPV), but interestingly only a small portion develop cervical cancer and in the remainder infection regresses to a normal healthy state. Beyond HPV status, associated molecular characterization of disease has to be established. However, initial work suggests the existence of several different molecular classes, based on the biological features of differentially expressed genes in each subtype. This suggests that additional risk factors play an important role in the outcome of infection. Host genomic factors play an important role in the outcome of such complex or multifactor diseases such as cervical cancer and are also known to regulate the rate of disease progression. The aim of this review was to compile advances in the field of host genomics of HPV positive and negative cervical cancer and their association with clinical response.

• Genomics & Informatics
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• v.16 no.4
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• pp.18.1-18.9
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• 2018

Long non-coding RNAs (lncRNAs) are classified as RNAs that are longer than 200 nucleotides and cannot be translated into protein. Several studies have demonstrated that lncRNAs are directly or indirectly involved in a variety of biological processes and in the regulation of gene expression. In addition, lncRNAs have important roles in many diseases including cancer. It has been shown that abnormal expression of lncRNAs is observed in several human solid tumors. Several studies have shown that many lncRNAs can function as oncogenes in cancer development through the induction of cell cycle progression, cell proliferation and invasion, anti-apoptosis, and metastasis. Oncogenic lncRNAs have the potential to become promising biomarkers and might be potent prognostic targets in cancer therapy. However, the biological and molecular mechanisms of lncRNA involvement in tumorigenesis have not yet been fully elucidated. This review summarizes studies on the regulatory and functional roles of oncogenic lncRNAs in the development and progression of various types of cancer.

• BMB Reports
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• v.45 no.6
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• pp.365-370
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• 2012

Hepatitis B virus (HBV) DNA is often integrated into hepatocellular carcinoma (HCC). Although the relationship between HBV integration and HCC development has been widely studied, the role of HBV integration in HCC development is still not completely understood. In the present study, we constructed a pooled BAC library of 9 established cell lines derived from HCC patients with HBV infections. By amplifying viral genes and superpooling of BAC clones, we identified 2 clones harboring integrated HBV DNA. Screening of host-virus junctions by repeated sequencing revealed an HBV DNA integration site on chromosome 11q13 in the SNU-886 cell line. The structure and rearrangement of integrated HBV DNA were extensively analyzed. An inverted duplicated structure, with fusion of at least 2 HBV DNA molecules in opposite orientations, was identified in the region. The gene expression of cancer-related genes increased near the viral integration site in HCC cell line SNU-886.

• Molecules and Cells
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• v.45 no.8
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• pp.550-563
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• 2022

Hepatocellular carcinoma (HCC) is an aggressive and incurable cancer. Although understanding of the molecular pathogenesis of HCC has greatly advanced, therapeutic options for the disease remain limited. In this study, we demonstrated that SETD5 expression is positively associated with poor prognosis of HCC and that SETD5 depletion decreased HCC cell proliferation and invasion while inducing cell death. Transcriptome analysis revealed that SETD5 loss downregulated the interferon-mediated inflammatory response in HCC cells. In addition, SETD5 depletion downregulated the expression of a critical glycolysis gene, PKM (pyruvate kinase M1/2), and decreased glycolysis activity in HCC cells. Finally, SETD5 knockdown inhibited tumor growth in xenograft mouse models. These results collectively suggest that SETD5 is involved in the tumorigenic features of HCC cells and that targeting SETD5 may suppress HCC progression.