Cancer Research and Treatment

Original Articles

Sarcoma

Case Series of Soft Tissue Sarcoma Patients with Brain Metastasis with Implications from Genomic and Transcriptomic Analysis: Changhee Park, Rokhyun Kim, Jaeyong Choi, Miso Kim, Tae Min Kim, Ilkyu Han, Jong-Il Kim, Han-Soo Kim; Cancer Res Treat. 2024;56(2):665-674. Published online September 27, 2023; DOI: https://doi.org/10.4143/crt.2023.864

Abstract PDF Supplementary Material PubReader ePub: Purpose
Brain metastasis rarely occurs in soft tissue sarcoma (STS). Here, we present five cases of STS with brain metastases with genetic profiles.
Materials and Methods
We included five patients from Seoul National University Hospital who were diagnosed with STS with metastasis to the brain. Tissue from the brain metastasis along with that from the primary site or other metastases were used for DNA and RNA sequencing to identify genetic profiles. Gene expression profiles were compared with sarcoma samples from The Cancer Genome Atlas.
Results
The overall survival after diagnosis of brain metastasis ranged from 2.2 to 34.3 months. Comparison of mutational profiles between brain metastases and matched primary or other metastatic samples showed similar profiles. In two patients, copy number variation profiles between brain metastasis and other tumors showed several differences including MYCL, JUN, MYC, and DDR2 amplification. Gene ontology analysis showed that the group of genes significantly highly expressed in the brain metastasis samples was enriched in the G-protein coupled receptor activity, structural constituent of chromatin, protein heterodimerization activity, and binding of DNA, RNA, and protein. Gene set enrichment analysis showed enrichment in the pathway of neuroactive ligand-receptor interaction and systemic lupus erythematosus.
Conclusion
The five patients had variable ranges of clinical courses and outcomes. Genomic and transcriptomic analysis of STS with brain metastasis implicates possible involvement of complex expression modification and epigenetic changes rather than the addition of single driver gene alteration.

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Lung and Thoracic cancer

Clinical Impact of Genomic and Pathway Alterations in Stage I EGFR-Mutant Lung Adenocarcinoma: Jae Seok Lee, Eun Kyung Kim, Kyung A Kim, Hyo Sup Shim; Cancer Res Treat. 2024;56(1):104-114. Published online July 24, 2023; DOI: https://doi.org/10.4143/crt.2023.728

Abstract PDF Supplementary Material PubReader ePub: Purpose
We investigated the clinical impact of genomic and pathway alterations in stage I epidermal growth factor receptor (EGFR)–mutant lung adenocarcinomas, which have a high recurrence rate despite complete surgical resection.
Materials and Methods
Out of the initial cohort of 257 patients with completely resected stage I EGFR-mutant lung adenocarcinoma, tumor samples from 105 patients were subjected to analysis using large-panel next-generation sequencing. We analyzed 11 canonical oncogenic pathways and determined the number of pathway alterations (NPA). Survival analyses were performed based on co-occurring alterations and NPA in three patient groups: all patients, patients with International Association for the Study of Lung Cancer (IASLC) pathology grade 2, and patients with recurrent tumors treated with EGFR–tyrosine kinase inhibitor (TKI).
Results
In the univariate analysis, pathological stage, IASLC grade, TP53 mutation, NPA, phosphoinositide 3-kinase pathway, p53 pathway, and cell cycle pathway exhibited significant associations with worse recurrence-free survival (RFS). Moreover, RPS6KB1 or EGFR amplifications were linked to a poorer RFS. Multivariate analysis revealed that pathologic stage, IASLC grade, and cell cycle pathway alteration were independent poor prognostic factors for RFS (p=0.002, p < 0.001, and p=0.006, respectively). In the grade 2 subgroup, higher NPA was independently associated with worse RFS (p=0.003). Additionally, in patients with recurrence treated with EGFR-TKIs, co-occurring TP53 mutations were linked to shorter progression-free survival (p=0.025).
Conclusion
Genomic and pathway alterations, particularly cell cycle alterations, high NPA, and TP53 mutations, were associated with worse clinical outcomes in stage I EGFR-mutant lung adenocarcinoma. These findings may have implications for risk stratification and the development of new therapeutic strategies in early-stage EGFR-mutant lung cancer patients.

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General

Clinicopathological Characteristics of NRG1 Fusion–Positive Solid Tumors in Korean Patients: Yoon Jin Cha, Chung Lee, Bio Joo, Kyung A Kim, Choong-kun Lee, Hyo Sup Shim; Cancer Res Treat. 2023;55(4):1087-1095. Published online June 15, 2023; DOI: https://doi.org/10.4143/crt.2023.682

Abstract PDF PubReader ePub

Purpose
Neuregulin 1 (NRG1) gene fusion is a potentially actionable oncogenic driver. The oncoprotein binds to ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic approach for inhibiting ERBB3/ERBB2. However, the frequency and clinicopathological features of solid tumors harboring NRG1 fusions in Korean patients remain largely unknown.
Materials and Methods
We reviewed archival data from next-generation sequencing panel tests conducted at a single institution, specifically selecting patients with in-frame fusions that preserved the functional domain. The clinicopathological characteristics of patients harboring NRG1 fusions were retrospectively reviewed.
Results
Out of 8,148 patients, NRG1 fusions were identified in 22 patients (0.27%). The average age of the patients was 59 years (range, 32 to 78 years), and the male-to-female ratio was 1:1.2. The lung was the most frequently observed primary site (n=13), followed by the pancreaticobiliary tract (n=3), gastrointestinal tract (n=2, stomach and rectum each), ovary (n=2), breast (n=1), and soft tissue (n=1). Histologically, all tumors demonstrated adenocarcinoma histology, with the exception of one case of sarcoma. CD74 (n=8) and SLC3A2 (n=4) were the most frequently identified fusion partners. Dominant features included the presence of fewer than three co-occurring genetic alterations, a low tumor mutation burden, and low programmed death-ligand 1 expression. Various clinical responses were observed in patients with NRG1 fusions.
Conclusion
Despite the rarity of NRG1 fusions in Korean patients with solid tumors, identification through next-generation sequencing enables the possibility of new targeted therapies.

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Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors
Chunwei Xu, Qian Wang, Dong Wang, Wenxian Wang, Wenfeng Fang, Ziming Li, Aijun Liu, Jinpu Yu, Wenzhao Zhong, Zhijie Wang, Yongchang Zhang, Jingjing Liu, Shirong Zhang, Xiuyu Cai, Anwen Liu, Wen Li, Ping Zhan, Hongbing Liu, Tangfeng Lv, Liyun Miao, Lingfen
Global Medical Genetics.2024; 11(01): 086. CrossRef
Analysis on the pathogenesis and treatment progress of NRG1 fusion-positive non-small cell lung cancer
Hongyan Li, Lina Xu, Hongshun Cao, Tianyi Wang, Siwen Yang, Yixin Tong, Linlin Wang, Qiang Liu
Frontiers in Oncology.2024;[Epub] CrossRef
Analysis of CD74 Occurrence in Oncogenic Fusion Proteins
Jasmine Vargas, Georgios Pantouris
International Journal of Molecular Sciences.2023; 24(21): 15981. CrossRef

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Gastrointestinal cancer

Clinical Application of Targeted Deep Sequencing in Metastatic Colorectal Cancer Patients: Actionable Genomic Alteration in K-MASTER Project: Youngwoo Lee, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Ah-reum Lim, Ju Won Kim, Yoon Ji Choi, Kyong Hwa Park, Yeul Hong Kim; Cancer Res Treat. 2021;53(1):123-130. Published online August 18, 2020; DOI: https://doi.org/10.4143/crt.2020.559

Abstract PDF Supplementary Material PubReader ePub

Purpose
Next-generation sequencing (NGS) can facilitate precision medicine approaches in metastatic colorectal cancer (mCRC) patients. We investigated the molecular profiling of Korean mCRC patients under the K-MASTER project which was initiated in June 2017 as a nationwide precision medicine oncology clinical trial platform which used NGS assay to screen actionable mutations.
Materials and Methods
As of 22 January 2020, total of 994 mCRC patients were registered in K-MASTER project. Targeted sequencing was performed using three platforms which were composed of the K-MASTER cancer panel v1.1 and the SNUH FIRST Cancer Panel v3.01. If tumor tissue was not available, cell-free DNA was extracted and the targeted sequencing was performed by Axen Cancer Panel as a liquid biopsy.
Results
In 994 mCRC patients, we found 1,564 clinically meaningful pathogenic variants which mutated in 71 genes. Anti-EGFR therapy candidates were 467 patients (47.0%) and BRAF V600E mutation (n=47, 4.7%), deficient mismatch repair/microsatellite instability–high (n=15, 1.5%), HER2 amplifications (n=10, 1.0%) could be incorporated with recently approved drugs. The patients with high tumor mutation burden (n=101, 12.7%) and DNA damaging response and repair defect pathway alteration (n=42, 4.2%) could be enrolled clinical trials with immune checkpoint inhibitors. There were more colorectal cancer molecular alterations such as PIK3CA, KRAS G12C, atypical BRAF, and HER2 mutations and even rarer but actionable genes that approved or ongoing clinical trials in other solid tumors.
Conclusion
K-MASTER project provides an intriguing background to investigate new clinical trials with biomarkers and give therapeutic opportunity for mCRC patients.

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Tumor mutational burden in colorectal cancer: Implications for treatment
Adriana Marques, Patrícia Cavaco, Carla Torre, Bruno Sepodes, João Rocha
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Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer
Yonghwa Choi, Jangwoo Lee, Keewon Shin, Ji Won Lee, Ju Won Kim, Soohyeon Lee, Yoon Ji Choi, Kyong Hwa Park, Jwa Hoon Kim
BMC Cancer.2024;[Epub] CrossRef
PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
Cancer Research and Treatment.2023; 55(2): 531. CrossRef
Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer
Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
Scientific Reports.2023;[Epub] CrossRef
Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations
Yoon Ji Choi, Jung Yoon Choi, Ju Won Kim, Ah Reum Lim, Youngwoo Lee, Won Jin Chang, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Jong Won Lee, Eun Joo Kang, Jung Sun Kim, Taekyu Lim, Hye Sook Kim, Yu Jung Kim, Mi Sun Ahn, Young Saing Kim, Ji Hyun Park, Se
Cancer Research and Treatment.2022; 54(1): 30. CrossRef
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Molecular Biology Reports.2022; 49(2): 1341. CrossRef
Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se
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Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Koung Jin Suh, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, Jae Ho Byun, Jin Hyun Park, Gyeong-Won L
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Paired analysis of tumor mutation burden calculated by targeted deep sequencing panel and whole exome sequencing in non-small cell lung cancer
Sehhoon Park, Chung Lee, Bo Mi Ku, Minjae Kim, Woong-Yang Park, Nayoung K. D. Kim, Myung-Ju Ahn
BMB Reports.2021; 54(7): 386. CrossRef
Evaluation of a Targeted Next-Generation Sequencing Panel for the Non-Invasive Detection of Variants in Circulating DNA of Colorectal Cancer
Aitor Rodríguez-Casanova, Aida Bao-Caamano, Ramón M. Lago-Lestón, Elena Brozos-Vázquez, Nicolás Costa-Fraga, Isabel Ferreirós-Vidal, Ihab Abdulkader, Yolanda Vidal-Insua, Francisca Vázquez Rivera, Sonia Candamio Folgar, Rafael López-López, Laura Muinelo-R
Journal of Clinical Medicine.2021; 10(19): 4487. CrossRef
Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer
Saikat Chowdhury, Matan Hofree, Kangyu Lin, Dipen Maru, Scott Kopetz, John Paul Shen
Cancers.2021; 13(19): 4923. CrossRef

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Clinical Implication of Concordant or Discordant Genomic Profiling between Primary and Matched Metastatic Tissues in Patients with Colorectal Cancer: Jung Yoon Choi, Sunho Choi, Minhyeok Lee, Young Soo Park, Jae Sook Sung, Won Jin Chang, Ju Won Kim, Yoon Ji Choi, Jin Kim, Dong-Sik Kim, Sung-Ho Lee, Junhee Seok, Kyong Hwa Park, Seon Hahn Kim, Yeul Hong Kim; Cancer Res Treat. 2020;52(3):764-778. Published online February 16, 2020; DOI: https://doi.org/10.4143/crt.2020.044

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to identify the concordant or discordant genomic profiling between primary and matched metastatic tumors in patients with colorectal cancer (CRC) and to explore the clinical implication.
Materials and Methods
Surgical samples of primary and matched metastatic tissues from 158 patients (335 samples) with CRC at Korea University Anam Hospital were evaluated using the Ion AmpliSeq Cancer Hotspot Panel. We compared genetic variants and classified them as concordant, primary-specific, and metastasis-specific variants. We used a combination of principal components analysis and clustering to find genomic groups. Kaplan-Meier curves were used to appraise survival between genomic groups. We used machine learning to confirm the correlation between genetic variants and metastatic sites.
Results
A total of 282 types of deleterious non-synonymous variants were selected for analysis. Of a total of 897 variants, an average of 40% was discordant. Three genomic groups were yielded based on the genomic discrepancy patterns. Overall survival differed significantly between the genomic groups. The poorest group had the highest proportion of concordant KRAS G12V and additional metastasis-specific SMAD4. Correlation analysis between genetic variants and metastatic sites suggested that concordant KRAS mutations would have more disseminated metastases.
Conclusion
Driver gene mutations were mostly concordant; however, discordant or metastasis-specific mutations were present. Clinically, the concordant driver genetic changes with additional metastasis-specific variants can predict poor prognosis for patients with CRC.

Citations

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Gene-Mutation-Based Algorithm for Prediction of Treatment Response in Colorectal Cancer Patients
Heather Johnson, Zahra El-Schich, Amjad Ali, Xuhui Zhang, Athanasios Simoulis, Anette Gjörloff Wingren, Jenny L. Persson
Cancers.2022; 14(8): 2045. CrossRef
Putative anoikis resistant subpopulations are enriched in lymph node metastases and indicate adverse prognosis in colorectal carcinoma
Taneli T. Mattila, Madhura Patankar, Juha P. Väyrynen, Kai Klintrup, Jyrki Mäkelä, Anne Tuomisto, Pentti Nieminen, Markus J. Mäkinen, Tuomo J. Karttunen
Clinical & Experimental Metastasis.2022; 39(6): 883. CrossRef
Clinical Application of Targeted Deep Sequencing in Metastatic Colorectal Cancer Patients: Actionable Genomic Alteration in K-MASTER Project
Youngwoo Lee, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Ah-reum Lim, Ju Won Kim, Yoon Ji Choi, Kyong Hwa Park, Yeul Hong Kim
Cancer Research and Treatment.2021; 53(1): 123. CrossRef
Comparison of metastatic castration-resistant prostate cancer in bone with other sites: clinical characteristics, molecular features and immune status
Zhengquan Xu, Yanhong Ding, Wei Lu, Ke Zhang, Fei Wang, Guanxiong Ding, Jianqing Wang
PeerJ.2021; 9: e11133. CrossRef
High Concordance of Genomic Profiles between Primary and Metastatic Colorectal Cancer
Seung Eun Lee, Ha Young Park, Dae-Yong Hwang, Hye Seung Han
International Journal of Molecular Sciences.2021; 22(11): 5561. CrossRef
Comprehensive Imaging Characterization of Colorectal Liver Metastases
Drew Maclean, Maria Tsakok, Fergus Gleeson, David J. Breen, Robert Goldin, John Primrose, Adrian Harris, James Franklin
Frontiers in Oncology.2021;[Epub] CrossRef

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Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients: Se-Hoon Lee, Boram Lee, Joon Ho Shim, Kwang Woo Lee, Jae Won Yun, Sook-Young Kim, Tae-You Kim, Yeul Hong Kim, Young Hyeh Ko, Hyun Cheol Chung, Chang Sik Yu, Jeeyun Lee, Sun Young Rha, Tae Won Kim, Kyung Hae Jung, Seock-Ah Im, Hyeong-Gon Moon, Sukki Cho, Jin Hyoung Kang, Jihun Kim, Sang Kyum Kim, Han Suk Ryu, Sang Yun Ha, Jong Il Kim, Yeun-Jun Chung, Cheolmin Kim, Hyung-Lae Kim, Woong-Yang Park, Dong-Young Noh, Keunchil Park; Cancer Res Treat. 2019;51(1):211-222. Published online April 23, 2018; DOI: https://doi.org/10.4143/crt.2018.132

Abstract PDF Supplementary Material PubReader ePub

Purpose
With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data.
Materials and Methods
To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared.
Results
We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration.
Conclusion
In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

Citations

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Real-World Data and Clinical Implications of Next-Generation Sequencing (NGS)-Based Analysis in Metastatic Breast Cancer Patients
Fabio Canino, Antonio Tornincasa, Stefania Bettelli, Samantha Manfredini, Monica Barbolini, Luca Moscetti, Claudia Omarini, Angela Toss, Fabio Tamburrano, Giuseppina Antonelli, Federica Baglio, Lorenzo Belluzzi, Giulio Martinelli, Salvatore Natalizio, Orn
International Journal of Molecular Sciences.2024; 25(5): 2490. CrossRef
Exploring the DNA methylome of Korean patients with colorectal cancer consolidates the clinical implications of cancer-associated methylation markers
Sejoon Lee, Kil-yong Lee, Ji-Hwan Park, Duck-Woo Kim, Heung-Kwon Oh, Seong-Taek Oh, Jongbum Jeon, Dongyoon Lee, Soobok Joe, Hoang Bao Khanh Chu, Jisun Kang, Jin-Young Lee, Sheehyun Cho, Hyeran Shim, Si-Cho Kim, Hong Seok Lee, Young-Joon Kim, Jin Ok Yang,
BMB Reports.2024; 57(3): 161. CrossRef
Establishing molecular pathology curriculum for pathology trainees and continued medical education: a collaborative work from the Molecular Pathology Study Group of the Korean Society of Pathologists
Jiwon Koh, Ha Young Park, Jeong Mo Bae, Jun Kang, Uiju Cho, Seung Eun Lee, Haeyoun Kang, Min Eui Hong, Jae Kyung Won, Youn-La Choi, Wan-Seop Kim, Ahwon Lee
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IC Uzoma, IA Taiwo, NI Ugwu, MA Durosinmi, O Akinloye
Nigerian Journal of Clinical Practice.2023; 26(12): 1854. CrossRef
Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se
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Koung Jin Suh, Se Hyun Kim, Yu Jung Kim, Heechul Shin, Eunyoung Kang, Eun-Kyu Kim, Sejoon Lee, Ji Won Woo, Hee Young Na, Soomin Ahn, Bum-Sup Jang, In Ah Kim, So Yeon Park, Jee Hyun Kim
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Jwa Hoon Kim, Shinkyo Yoon, Dae Ho Lee, Se Jin Jang, Sung‐Min Chun, Sang‐We Kim
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Byung-Joo Min, Woo Seung Lee, Myung-Eui Seo, Kye-Hwa Lee, Seung-Yong Jeong, Ja-Lok Ku, Yeul Hong Kim, Sang-Won Shin, Ju Han Kim
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Paired Primary and Metastatic Tumor Analysis of Somatic Mutations in Synchronous and Metachronous Colorectal Cancer: Kyu-pyo Kim, Jeong-Eun Kim, Yong Sang Hong, Sung-Min Ahn, Sung Min Chun, Seung-Mo Hong, Se Jin Jang, Chang Sik Yu, Jin Cheon Kim, Tae Won Kim; Cancer Res Treat. 2017;49(1):161-167. Published online July 4, 2016; DOI: https://doi.org/10.4143/crt.2015.490

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although the mutation status of KRAS is highly concordant in primary and metastatic lesions, it has not been generalized to other major pathway genes.
Materials and Methods
In this study, 41 genes were evaluated and the mutational profiles were compared in 46 colorectal cancer patients with paired surgical specimens of primary and metastatic lesions: synchronous (n=27) and metachronous (n=19) lesions. A high-throughput mass spectrometry-based genotyping platform validated by orthogonal chemistry, OncoMap v.4.4, was used to evaluate the formalin-fixed, paraffin-embedded surgical specimens. The patients’ demographics, tumor characteristics, and microsatellite instability status were analyzed by a retrospective chart review.
Results
In this study,with OncoMap, mutationswere identified in 80.4% of patientswith the following frequency: KRAS (39.1%), TP53 (28.3%), APC (28.3%), PIK3CA (6.5%), BRAF (6.5%), and NRAS (4.3%). Although 19.6% (9/46) of the patients showed no gene mutations, 43.5% (20/46) and 37.0% (17/46) had mutations in one and two or more genes, respectively. The synchronous and metachronous lesions showed similar mutational profiles. Paired samples between primary and metastatic tumors differed in 7.4% (2/27) and 10.5% (2/19) for synchronous and metachronous according to OncoMap.
Conclusion
These findings indicate the major pathway genes, including KRAS, TP53, APC, PIK3CA, BRAF, and NRAS, are often concordant between the primary and metastatic lesions regardless of the temporal relationship of metastasis.

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Review Article

Systems Biology Approaches to Decoding the Genome of Liver Cancer: Ju-Seog Lee, Ji Hoon Kim, Yun-Yong Park, Gordon B. Mills; Cancer Res Treat. 2011;43(4):205-211. Published online December 27, 2011; DOI: https://doi.org/10.4143/crt.2011.43.4.205

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Molecular classification of cancers has been significantly improved patient outcomes through the implementation of treatment protocols tailored to the abnormalities present in each patient's cancer cells. Breast cancer represents the poster child with marked improvements in outcome occurring due to the implementation of targeted therapies for estrogen receptor or human epidermal growth factor receptor-2 positive breast cancers. Important subtypes with characteristic molecular features as potential therapeutic targets are likely to exist for all tumor lineages including hepatocellular carcinoma (HCC) but have yet to be discovered and validated as targets. Because each tumor accumulates hundreds or thousands of genomic and epigenetic alterations of critical genes, it is challenging to identify and validate candidate tumor aberrations as therapeutic targets or biomarkers that predict prognosis or response to therapy. Therefore, there is an urgent need to devise new experimental and analytical strategies to overcome this problem. Systems biology approaches integrating multiple data sets and technologies analyzing patient tissues holds great promise for the identification of novel therapeutic targets and linked predictive biomarkers allowing implementation of personalized medicine for HCC patients.

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Erratum

ERRATUM: Correction for Incorrect Citation of Reference and Wording in a Table: Cancer Res Treat. 2011;43(3):204-204. Published online September 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.3.204

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Review Article

The Role of HPV E6 and E7 Oncoproteins in HPV-associated Cervical Carcinogenesis: Eun-Kyoung Yim, Jong-Sup Park; Cancer Res Treat. 2005;37(6):319-324. Published online December 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.6.319

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Cervical cancer is one of the leading world causes of cancer morbidity and mortality in woman, with more than 98% related to a human papillomavirus (HPV) infection origin. Infection with specific subtypes of HPV has been strongly implicated in cervical carcinogenesis. The identification and functional verification of host proteins associated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis and the development of cervical cancer-specific markers. The advent of functional genomics and proteomics has provided hope of discovering novel biological markers for use in the screening, early diagnosis, prognostication and prediction of response to therapy. Herein, we review the studies where the profiles of host proteins associated with HPV E6 and E7 oncoproteins in cervical cancer were generated.

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Original Article

Identification of Genes Involved in Liver Cancer Cell Growth Using an Antisense Library of Phage Genomic DNA: Yun Han Lee, Young Ho Kim, Jong Gu Park; Cancer Res Treat. 2004;36(4):246-254. Published online August 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.4.246

Abstract PDF PubReader ePub: Purpose
Genes involved in liver cancer cell growth have been identified using an antisense library of large circular (LC-) genomic DNA of a recombinant M13 phage.
Materials and Methods
A subtracted cDNA library was constructed by combining procedures of suppression subtractive hybridization (SSH) and unidirectional cloning of the subtracted cDNA into an M13 phagemid vector. Utilizing the life cycle of M13 bacteriophages, LC-antisense molecules derived from 1,200 random cDNA clones selected by size were prepared from the culture supernatant of bacterial transformants. The antisense molecules were arrayed for transfection on 96-well plates preseeded with HepG2.
Results
When examined for growth inhibition after antisense transfection, 153 out of 1,200 LC-antisense molecules showed varying degrees of growth inhibitory effect to HepG2 cells. Sequence comparison of the 153 clones identified 58 unique genes. The observations were further extended by other cell-based assays.
Conclusion
These results suggest that the LC-antisense library offers potential for unique high-throughput screening to find genes involved in a specific biological function, and may prove to be an effective target validation system for gene-based drug discovery.

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