Our current research mainly focuses on the identification and characterization of novel mutations and epigenetic alterations of tumor suppressor genes or oncogenes in lymphoid cancers. Our interest mainly resides in lymphomas (e.g. follicular lymphoma) and other lymphoid cancers (e.g. multiple myeloma) which are neoplastic diseases having a high degree of genetic heterogeneity.
We frequently use next generation sequencing (NGS) based technologies (e.g. WES, RNA-Seq, targeted NGS) to generate a candidate list of aberrant genes using panels of lymphoma patient samples. We then cross-validate mutations that are identified through NGS methodologies by applying Sanger sequencing. Moreover, our studies focus on genome-wide or loci-specific methylation changes in cancer samples. Altogether, we characterize these aberrations using a combination of genetic, epigenetic and molecular biology assays. In general, our studies follow a wholistic approach which involves the cooperation of a variety interrelated biomedical disciplines such as pathology, functional genomics, and computational bioinformatics. Our eventual goal is to identify and characterize genetic and epigenetic abnormalities in individual cancer patients to translate the discoveries as personalized medicine.
Assoc. Prof. Dr. Can Küçük earned 40.000 USD project award of the ASH Awards Supplement Program from the American Society of Hematology (ASH), which is the largest professional society of hematology in the world. The awardees for the ASH Supplement Award were selected among previous winners with ongoing projects of ASH awards in 5 different categories including prestigous awards such as the ASH Global Research Award and ASH Scholar Award. ASH Supplement Award is the 2nd award from the ASH in its 64 years of history to a scientist working in Turkey after the ASH Global Research Award that was also provided to Dr. Can Küçük in 2018. You can obtain more information regarding this award program through the following link: https://www.hematology.org/awards/career-enhancement-and-training/ash-awards-supplement-program
IL2 signaling plays a crucial role during NK cell activation including proliferation as a response to virus-infected cells or neoplastic cells. Appropriate termination of IL2 signaling is required to control NK cell expansion and prevent NK cell malignancies. The molecular mechanisms responsible for termination of IL2 signaling were largely unknown. An international collaborative study from Dr. Küçük’s research group revealed that PRDM1 decreases sensitivity of NK cells to IL2 cytokine through direct transcriptional inhibition of IL2RA, thereby preventing uncontrolled NK cell expansion.
From Lymphoid Cancer Genomics Research Group Dr. Burcu Akman, Dr. Xiaozhou Hu, Tevfik Hatipoğlu, and Dr. Can Küçük contributed to this study, which has been highlighted in the recent issue of the Journal of Leukocyte Biology. For more information, please see the following link: https://jlb.onlinelibrary.wiley.com/
Altun Z, Yuan H, Baran B, Aktaş S, Esmeray Sönmez E, Küçük C, Olgun N. Whole-exome sequencing reveals genetic variants in low-risk and high-risk neuroblastoma.. Gene. 2023 April ; 860 : 147233. doi:10.1016/j.gene.2023.147233. Download
Ahmet Şeyhanlı, Tevfik Hatipoğlu, Burcu Akman, Xiaozhou Hu, Güner Hayri Özsan, Can Küçük. Genetic and Epigenetic Analyses Reveal Transcriptional Silencing of SOX7 due to Deletion in a Multiple Myeloma Case with Double Relapse. International Journal of Hematology and Oncology. 2023 April ; 33 (1306-133X) : 054-056. doi:10.4999/uhod.236587. Download
Hatipoğlu T, Esmeray Sönmez E, Hu X, Yuan H, Danyeli AE, Şeyhanlı A, Önal-Süzek T, Zhang W, Akman B, Olgun A, Özkal S, Alacacıoğlu İ, Özcan MA, You H, Küçük C. Plasma Concentrations and Cancer-Associated Mutations in Cell-Free Circulating DNA of Treatment-Naive Follicular Lymphoma for Improved Non-Invasive Diagnosis and Prognosis.. Frontiers in Oncology. 2022 June ; 12 : 870487. doi:10.3389/fonc.2022.870487. Download
Esmeray Sönmez, Esra, Tevfik Hatipoğlu, Deniz Kurşun, Xiaozhou Hu, Burcu Akman, Hongling Yuan, Ayça Erşen Danyeli, İnci Alacacıoğlu, Sermin Özkal, Aybüke Olgun, Taner Kemal Erdağ, Hua You, and Can Küçük. Whole Transcriptome Sequencing Reveals Cancer-Related, Prognostically Significant Transcripts and Tumor-Infiltrating Immunocytes in Mantle Cell Lymphoma. Cells. 2022 October ; 11 (21) : 3394. doi:10.3390/cells11213394. Download
Mengyuan Dai, Miao Liu, Hua Yang, Can Küçük, Hua You. New insights into epigenetic regulation of resistance to PD-1/PD-L1 blockade cancer immunotherapy: mechanisms and therapeutic opportunities. Experimental hematology & oncology. 2022 November . doi:10.1186/s40164-022-00356-0. Download
Wang Y, Ba HJ, Wen XZ, Zhou M, Küçük C, Tamagnone L, Wei L, You H. A prognostic model for melanoma patients on the basis of immune-related lncRNAs.. Aging. 2021 March ; 13 . doi:10.18632/aging.202730. Download
Yılmaz H, Toy HI, Marquardt S, Karakülah G, Küçük C, Kontou PI, Logotheti S, Pavlopoulou A. In Silico Methods for the Identification of Diagnostic and Favorable Prognostic Markers in Acute Myeloid Leukemia.. International journal of molecular sciences. 2021 September ; 22 (17) : 9601. doi:10.3390/ijms22179601. Download
Küçük C. Genetic susceptibility to natural killer T-cell lymphoma.. The Lancet. Oncology. 2020 February ; 21 (2) : 196-197. doi:10.1016/S1470-2045(19)30820-4. Download
Esmeray E, Küçük C. Genetic alterations in B cell lymphoma subtypes as potential biomarkers for noninvasive diagnosis, prognosis, therapy, and disease monitoring.. Turkish journal of biology = Turk biyoloji dergisi. 2020 February ; 44 (1) : 1-14. doi:10.3906/biy-1908-23. Download
Akman B, Hu X, Liu X, Hatipoğlu T, You H, Chan WC, Küçük C. PRDM1 decreases sensitivity of human NK cells to IL2-induced cell expansion by directly repressing CD25 (IL2RA).. Journal of leukocyte biology. 2020 November . doi:10.1002/JLB.2A0520-321RR. Download
Küçük C, Wei L, You H. Indolent T-Cell Lymphoproliferative Disease of the GI Tract: Insights for Better Diagnosis, Prognosis, and Appropriate Therapy.. Frontiers in oncology. 2020 August ; 10 : 1276. doi:10.3389/fonc.2020.01276. Download
Küçük C, Wang J, Xiang Y, You H. Epigenetic aberrations in natural killer/T-cell lymphoma: diagnostic, prognostic and therapeutic implications.. Therapeutic advances in medical oncology. 2020 February ; 12 : 1758835919900856. doi:10.1177/1758835919900856. Download
Kursun, Deniz; Kucuk, Can. Systematic analysis of the frequently amplified 2p15-p16.1 locus reveals PAPOLG as a potential proto-oncogene in follicular and transformed follicular lymphoma. TURKISH JOURNAL OF BIOLOGY. 2019 ; 43 (2) . doi:10.3906/biy-1810-2. Download
Wan Y, He D, Ye Y, Zhang W, Zhao S, Long Y, Chen M, Küçük C. Primary cardiac diffuse large B-cell lymphoma with concurrent high MYC and BCL2 expression in an immunocompetent Chinese elderly woman. Cardiovasc Pathol. 2017 November ; 31 : 54-56. doi:10.1016/j.carpath.2017.07.006. Download
Hu X, Baytak E, Li J, Akman B, Okay K, Hu G, Scuto A, Zhang W, Küçük C. The relationship of REL proto-oncogene to pathobiology and chemoresistance in follicular and transformed follicular lymphoma. Leuk Res. 2017 March ; 54 : 30-38. doi:10.1016/j.leukres.2017.01.001. Download
Baytak E, Gong Q, Akman B, Yuan H, Chan WC, Küçük C. Whole transcriptome analysis reveals dysregulated oncogenic lncRNAs in natural killer/T-cell lymphoma and establishes MIR155HG as a target of PRDM1.. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2017 May ; 39 (5) : 1010428317701648. doi:10.1177/1010428317701648. Download
Gao, Li-Min; Zhao, Sha; Liu, Wei-Ping; Zhang, Wen-Yan; Li, Gan-Di; Kucuk, Can; Hu, Xiao-Zhou; Chan, Wing C.; Tang, Yuan; Ding, Wen-Shuang; Yan, Jia-Qi; Yao, Wen-Qing; Wang, Jian Chao. Clinicopathologic Characterization of Aggressive Natural Killer Cell Leukemia Involving Different Tissue Sites. AMERICAN JOURNAL OF SURGICAL PATHOLOGY. 2016 June ; 40 (6) : 836-846. doi:10.1097/PAS.0000000000000634. Download
Kucuk, Can; Hu, Xiaozhou; Gong, Qiang; Jiang, Bei; Cornish, Adam; Gaulard, Philippe; McKeithan, Timothy; Chan, Wing C.. Diagnostic and Biological Significance of KIR Expression Profile Determined by RNA-Seq in Natural Killer/T-Cell Lymphoma. AMERICAN JOURNAL OF PATHOLOGY. 2016 June ; 186 (6) : 1435-1441. doi:10.1016/j.ajpath.2016.02.011. Download
Hu X, Chan WC, Kücük C. Generation of a genetically engineered aggressive nk-cell leukemia cell line with stable IL2 expression. Acta Medica International. 2015 July ; 2 (2) : 78-84. doi:10.5530/ami.2015.3.6. Download
Küçük C, Jiang B, Hu X, Zhang W, Chan JK, Xiao W, Lack N, Alkan C, Williams JC, Avery KN, Kavak P, Scuto A, Sen E, Gaulard P, Staudt L, Iqbal J, Zhang W, Cornish A, Gong Q, Yang Q, Sun H, d'Amore F, Leppä S, Liu W, Fu K, de Leval L, McKeithan T, Chan WC. Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells.. Nature communications. 2015 January ; 6 : 6025. doi:10.1038/ncomms7025. Download
Küçük C, Hu X, Jiang B, Klinkebiel D, Geng H, Gong Q, Bouska A, Iqbal J, Gaulard P, McKeithan TW, Chan WC. Global promoter methylation analysis reveals novel candidate tumor suppressor genes in natural killer cell lymphoma.. Clinical cancer research : an official journal of the American Association for Cancer Research. 2015 April ; 21 (7) : 1699-711. doi:10.1158/1078-0432.CCR-14-1216. Download
Bouska A, McKeithan TW, Deffenbacher KE, Lachel C, Wright GW, Iqbal J, Smith LM, Zhang W, Kucuk C, Rinaldi A, Bertoni F, Fitzgibbon J, Fu K, Weisenburger DD, Greiner TC, Dave BJ, Gascoyne RD, Rosenwald A, Ott G, Campo E, Rimsza LM, Delabie J, Jaffe ES, Braziel RM, Connors JM, Staudt LM, Chan WC. Genome-wide copy-number analyses reveal genomic abnormalities involved in transformation of follicular lymphoma.. Blood. 2014 March ; 123 (11) : 1681-90. doi:10.1182/blood-2013-05-500595. Download
Küçük C, Hu X, Iqbal J, Gaulard P, Klinkebiel D, Cornish A, Dave BJ, Chan WC. HACE1 is a tumor suppressor gene candidate in natural killer cell neoplasms.. The American journal of pathology. 2013 January ; 182 (1) : 49-55. doi:10.1016/j.ajpath.2012.09.012. Download
Perry AM, Warnke RA, Hu Q, Gaulard P, Copie-Bergman C, Alkan S, Wang HY, Cheng JX, Bacon CM, Delabie J, Ranheim E, Kucuk C, Hu X, Weisenburger DD, Jaffe ES, Chan WC. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract.. Blood. 2013 November ; 122 (22) : 3599-606. doi:10.1182/blood-2013-07-512830. Download
Liu C, Iqbal J, Teruya-Feldstein J, Shen Y, Dabrowska MJ, Dybkaer K, Lim MS, Piva R, Barreca A, Pellegrino E, Spaccarotella E, Lachel CM, Kucuk C, Jiang CS, Hu X, Bhagavathi S, Greiner TC, Weisenburger DD, Aoun P, Perkins SL, McKeithan TW, Inghirami G, Chan WC. MicroRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma.. Blood. 2013 September ; 122 (12) : 2083-92. doi:10.1182/blood-2012-08-447375. Download
Cairns RA, Iqbal J, Lemonnier F, Kucuk C, de Leval L, Jais JP, Parrens M, Martin A, Xerri L, Brousset P, Chan LC, Chan WC, Gaulard P, Mak TW. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma.. Blood. 2012 February ; 119 (8) : 1901-3. doi:10.1182/blood-2011-11-391748. Download
Küçük C, Iqbal J, Hu X, Gaulard P, De Leval L, Srivastava G, Au WY, McKeithan TW, Chan WC. PRDM1 is a tumor suppressor gene in natural killer cell malignancies.. Proceedings of the National Academy of Sciences of the United States of America. 2011 December ; 108 (50) : 20119-24. doi:10.1073/pnas.1115128108. Download
Iqbal J, Weisenburger DD, Chowdhury A, Tsai MY, Srivastava G, Greiner TC, Kucuk C, Deffenbacher K, Vose J, Smith L, Au WY, Nakamura S, Seto M, Delabie J, Berger F, Loong F, Ko YH, Sng I, Liu X, Loughran TP, Armitage J, Chan WC, International Peripheral T-cell Lymphoma Project.. Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro.. Leukemia. 2011 February ; 25 (2) : 348-58. doi:10.1038/leu.2010.255. Download
Iqbal J, Kucuk C, Deleeuw RJ, Srivastava G, Tam W, Geng H, Klinkebiel D, Christman JK, Patel K, Cao K, Shen L, Dybkaer K, Tsui IF, Ali H, Shimizu N, Au WY, Lam WL, Chan WC. Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies.. Leukemia. 2009 June ; 23 (6) : 1139-51. doi:10.1038/leu.2009.3. Download
Total : 29
Genomik ve Uygulamaları (2023). Moleküler Biyoloji ve Genetik (Sağlık Alanında ve Biyoteknolojide Uygulamalar). TÜBA.
Lenfoma Genetiği (HL, NHL, B-cell lenfoma, KLL) (2019). HematoLog-Genetik. Galenos Yayınevi.
Total : 2
The Scientific and Technological Research Council of Turkey - TUBITAK - RD : REL Onkogeninin Foliküler Lenfoma Oluşumundaki Rolünün İncelenmesi, Finished
The Scientific and Technological Research Council of Turkey - TUBITAK - RD : Investigation of the Potential of the Mutations in Cell-free Circulating Tumor DNA as Biomarkers of Diagnosis and Chemo-immunotheraphy Resistance in Follicular Lymphoma Patients, Finished
The Scientific and Technological Research Council of Turkey - TUBITAK - RD : Identification of long non-coding RNAs that have potential to be novel diagnostic, prognostic biomarkers or therapeutic targets in mantle cell lymphoma through whole-transcriptome sequencing, Finished