Although bibliometric analyses have been performed in the past on cancer and genomics, little is known about the most frequently cited articles specifically related to cancer epigenetics. Therefore, the purpose of this study is to use citation count to identify those papers in the scientific literature that have made key contributions in the field of cancer epigenetics and identify key driving forces behind future investigations.
Materials and methods
The Thomas Reuters Web of Science services was queried for the years 1980-2018 without language restrictions. Articles were sorted in descending order of the number of times they were cited in the Web of Science database by other studies, and all titles and abstracts were screened to identify the research areas of the top 100 articles. The number of citations per year was calculated.
We identified the 100 most-cited articles on cancer epigenetics, which collectively had been cited 147,083 times at the time of this writing. The top-cited article was cited 7,124 times, with an average of 375 citations per year since publication. In the period 1980-2018, the most prolific years were the years 2006 and 2010, producing nine articles, respectively. Twenty-eight unique journals contributed to the 100 articles, with the Nature journal contributing most of the articles (n=22). The most common country of article origin was the United States of America (n=78), followed by Germany (n=4), Switzerland (n=4), Japan (n=3), Spain (n=2), and United Kingdom (n=2).
In this study, the 100 most-cited articles in cancer epigenetics were examined, and the contributions from various authors, specialties, and countries were identified. Cancer epigenetics is a rapidly growing scientific field impacting translational research in cancer screening, diagnosis, classification, prognosis, and targeted treatments. Recognition of important historical contributions to this field may guide future investigations.
In 1942, Conrad Hal Waddington was the first to use the Greek word “epigenesis”, to describe how cells differentiated, and thus epigenetics was coined to mean "the causal interactions between genes and their products which bring the phenotype into being" . But it was not until the 1970s when the contemporary definition emerged as “a hereditable change in gene expression that occurred without a change in the DNA sequence” . Broadly speaking, as it applies to modern cancer biology, epigenetics now refers to regulatory mechanisms of DNA transcription that affect gene expression of which DNA methylation is the most widely studied. The relative role of epigenetics in cancer has been attributed to the observation in 1983 by two laboratories that most cancer DNA has fewer methyl groups than non-cancer DNA [3-5]. In one of these studies, Feinberg and Vogelstein showed that DNA methylation was linked to tissue-specific gene silencing in cancer, by finding that a substantial proportion of CpG islands were methylated in normal tissues were unmethylated in cancer cells .
Citation analysis is a systematic approach for identifying scientific publications that have a high impact in the scientific or medical community measuring high-impact papers and how they have shaped scientific disciplines . For this purpose, the Institute for Scientific Information collects citation counts for academic journals in the Science Citation Index. Although bibliometric analyses have been performed in the past on cancer and genomics, little is known about the most frequently cited articles specifically related to cancer epigenetics [6-10]. Therefore, the purpose of this study is to use citation count to identify those papers in the scientific literature that have made key contributions in the field of cancer epigenetics and identify key driving forces behind future investigations.
Materials & Methods
The Thomson Reuters Web of Science (WoS) database was used to query for citations of all articles relevant to cancer epigenetics. The basic search tool was selected, the keyword search for the topic to identify the articles of interest was specified as: “(epigenetic OR epigenomic OR methylation OR hypermethylation OR CpG island OR chromatic remodeling OR histone modification OR RNA interference OR gene silencing OR promoter regions OR chromatin assembly and disassembly OR liquid biopsy OR molecular OR biomolecular) AND (cancer OR neoplasm)”. The following search parameters were used: 1) articles published in the years 1980-2018 (since the word "epigenetics" was conceived in 1980); 2) all languages; 3) within the Science Citation Index Expanded. The results were carefully reviewed, and only those relevant to cancer epigenetics were selected. All review articles were excluded from the list. The top 100 articles by the number of citations that matched the search criteria were then further analyzed, and the title, first author, journal, and year of publication, number of citations, country, and the institution of origin were recorded. The articles retrieved were sorted in descending order in terms of times cited, and the number of citations per year was calculated.
Our query retrieved 234,679 papers (Figure 1).
The top 100 articles related to “cancer epigenetics” were identified by the number of times they were cited (Table 1).
The articles on this top 100 list were cited between 7,124 times (article rank 1) and 720 times (article rank 100). Collectively, the top 100 articles have been cited 147,083 times with a median of 1,050 for each paper, and an interquartile range of 871 - 1610. The oldest article on the top 100 list was from 1993, and the most recent from 2016. In the period 1980-2018, the two most prolific years were 2006 and 2010, with nine articles each among the top 100 most cited articles. In terms of the number of citations per year, the top article had been cited 375 times per year (CY rank number 6). Likewise, the bottom article has been cited 29 times per year (CY rank number 100). A graph of time vs. publication output (Figure 1) indicates that the field of cancer epigenetics has had publications in the range 1994-2014. The most productive decade was from 2000 to 2009, producing 49 papers in the Top 100 (Table 2).
The top 100 most cited articles were published in 28 different journals, with the journal Nature contributing the most studies with 22 articles (Table 3).
Seventy-eight percent of the top 100 most cited papers originated in the United States (n=78). The next five countries with the highest number of articles were Germany (n=4), Switzerland (n=4), Japan (n=3), Spain (n=2), and United Kingdom (n=2). Australia, Belgium, Denmark, Israel, Netherlands, China, and South Korea had one article, each among the top 100. Among the 100 most cited papers, there were a total of 77 unique first authors. Collectively, the two authors with the largest number of articles on the top 100 list were Baylin SB and Herman JG with 26 and 20 papers, respectively (Table 4). The next five authors that followed were Getz G, Laird PW, Meyerson M, Sander C, and Weisenberger DJ, each with 13, 12, 12, 12, and 12 articles, respectively.
Among the top 100 cited papers, there were three clinical trials, two guidelines or society-based recommendations, 18 cancer classifications, 11 articles related to research tools or methods, 55 articles related to epigenetic cancer mechanism, nine papers related to epigenetic cancer markers/screening/diagnosis and five papers related to epigenetics and cancer treatment (Table 5).
In this study, we sought to identify the most cited 100 articles regarding cancer epigenetics, to gain insight into the history and future directions of this rapidly growing scientific field.
The article that received the most citations on the top 100 list was “Molecular classification of cancer: class discovery and class prediction by gene expression monitoring” . This paper was cited 7,340 times, with an average of 408 citations per year since publication. At the time, the paper was notable for developing the first generalized approach for identifying new cancer classes by applying gene expression profiling to distinguish between acute myeloid leukemia (AML) versus acute lymphoblastic leukemia (ALL). This study marked the beginning of gene expression-based cancer therapy. Currently, the European LeukemiaNet classification in AML uses cytogenetic and molecular data to identify the AML prognostic groups [12-14].
Since the first epigenetic abnormality was identified in cancer cells in 1983, multiple advances led to improved knowledge in epigenetics and cancer [3-5]. DNA methylation has been defined as an example of epigenetic dysregulation in cancer, with both hypomethylation and hyper-methylation having significant roles. DNA hypomethylation can lead to gene activation, and it is linked to chromosomal instability [15, 16]. DNA hypermethylation has been associated with gene silencing as a tumor-suppressor silencing cancer mechanism given that it has been found when genes are rarely mutated but that are frequently DNA hypermethylated and silenced in cancer [17-20]. Histone modification is another epigenetic cancer-linked mechanism that controls chromatin structure [21, 22]. As a result, the detection of epigenetic changes, such as abnormal promoter CpG island DNA hypermethylation, has been studied as a potential biomarker strategy for assessing cancer risk, early detection, prognosis and predicting therapeutic responses [23, 24]. The list of potential marker genes, knowledge of their position in cancer progression, and the development of ever more sensitive epigenetic detection strategies, including nanotechnology approaches, are all expanding [25, 26]. All these landmark discoveries led to the elucidation of novel cancer biomolecular mechanisms, new scientific research tools, and the development of new epigenetic-based targeted therapeutic avenues. As a result of that, “The National Institutes of Health (NIH) Roadmap Epigenomics Mapping Consortium” is accelerating the understanding of epigenomics in human health and disease together with the ENCODE Project (ENCyclopedia Of DNA Elements) [27, 28]. The most immediate future of this new exciting scientific field includes the development of liquid biopsies, personalized medicine, and targeted therapies.
Although citation analysis is a useful tool with the potential benefit of insight into literature trends, it is not without limitations. Over half a century has passed since the Science Citation Index (SCI) was launched as the first systematic effort to track citations in the scientific literature . We recognize that citation counts have inherent biases and that they are not purely quantifiable systems to rank papers by their impact in the scientific literature. In an attempt to control for some of these inherent and potential biases, we utilized the citations per year index in addition to the total number of citations per paper. Despite that, older publications have had a longer timespan to accumulate citations giving them a distinct advantage over newer and potentially more relevant studies. Lastly, one hundred is an arbitrary number since the landmark articles in epigenetic research did not accumulate enough citations such as the paper by Gama-Sosa, Slagel, Trewyn, et al. "The 5-methylcytosine content of DNA from human tumors" that only had 574 citations . Although metrics such as citation counts do have flaws, in the current era, they also serve as one way to measure objectively impact of an article in the scientific community.
In this study, the 100 most cited articles in cancer epigenetics were examined, and the contributions from various authors, specialties, and countries were identified. Cancer epigenetics is a rapidly growing scientific field impacting translational research in cancer screening, diagnosis, classification, prognosis, and targeted treatments. Recognition of important historical contributions to this field may guide future investigations.
- Waddington CH: The epigenotype. Int J Epidemiol. 2012, 41:10-13. 10.1093/ije/dyr184
- Richards EJ: Inherited epigenetic variation--revisiting soft inheritance. Nat Rev Genet. 2006, 7:395-401. 10.1038/nrg1834
- Feinberg AP, Vogelstein B: Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature. 1983, 301:89-92. 10.1038/301089a0
- Feinberg AP, Tycko B: The history of cancer epigenetics. Nat Rev Cancer. 2004, 4:143-153. 10.1038/nrc1279
- Jones PA, Baylin SB: The epigenomics of cancer. Cell. 2007, 128:683-692. 10.1016/j.cell.2007.01.029
- Van Noorden R, Maher B, Nuzzo R: The top 100 papers. Nature. 2014, 514:550-553. 10.1038/514550a
- Wrafter PF, Connelly TM, Khan J, Devane L, Kelly J, Joyce WP: The 100 most influential manuscripts in colorectal cancer: A bibliometric analysis. Surgeon. 2016, 14:327-336. 10.1016/j.surge.2016.03.001
- Uysal E: Top 100 cited classic articles in breast cancer research. Eur J Breast Health. 2017, 13:129-137.
- Powell AG, Hughes DL, Brown J, Larsen M, Witherspoon J, Lewis WG: Esophageal cancer's 100 most influential manuscripts: a bibliometric analysis. Dis Esophagus. 2017, 30:1-8. 10.1093/dote/dow039
- Guglielmi G: Wikipedia's top-cited scholarly articles - revealed. Nature. 2018, 557:291-292. 10.1038/d41586-018-05161-6
- Golub TR, Slonim DK, Tamayo P, et al.: Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science. 1999, 286:531-537. 10.1126/science.286.5439.531
- Dohner H, Estey EH, Amadori S, et al.: Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010, 115:453-474. 10.1182/blood-2009-07-235358
- Mrozek K, Marcucci G, Nicolet D, et al.: Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia. J Clin Oncol. 2012, 30:4515-4523. 10.1200/JCO.2012.43.4738
- Papaemmanuil E, Gerstung M, Bullinger L, et al.: Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016, 374:2209-2221. 10.1056/NEJMoa1516192
- Adorjan P, Distler J, Lipscher E, et al.: Tumour class prediction and discovery by microarray-based DNA methylation analysis. Nucleic Acids Res. 2002, 30:e21. 10.1093/nar/30.5.e21
- Eden A, Gaudet F, Waghmare A, Jaenisch R: Chromosomal instability and tumors promoted by DNA hypomethylation. Science. 2003, 300:455. 10.1126/science.1083557
- Greger V, Passarge E, Hopping W, Messmer E, Horsthemke B: Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma. Hum Genet. 1989, 83:155-158. 10.1007/bf00286709
- Hansen RS, Gartler SM: 5-Azacytidine-induced reactivation of the human X chromosome-linked PGK1 gene is associated with a large region of cytosine demethylation in the 5'CpG island. P Natl Acad Scad USA. 1990, 87:4174-4178. 10.1073/pnas.87.11.4174
- Herman JG, Latif F, Weng Y, et al.: Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. P Natl Acad Scad USA. 1994, 91:9700-9704. 10.1073/pnas.91.21.9700
- Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP: CpG island methylator phenotype in colorectal cancer. P Natl Acad Scad USA. 1999, 96:8681-8686. 10.1073/pnas.96.15.8681
- Buschhausen G, Wittig B, Graessmann M, Graessmann A: Chromatin structure is required to block transcription of the methylated herpes simplex virus thymidine kinase gene. P Natl Acad Scad USA. 1987, 84:1177-1181. 10.1073/pnas.84.5.1177
- Keshet I, Lieman-Hurwitz J, Cedar H: DNA methylation affects the formation of active chromatin. Cell. 1986, 44:535-543. 10.1016/0092-8674(86)90263-1
- Laird PW: The power and the promise of DNA methylation markers. Nat Rev Cancer. 2003, 3:253-266. 10.1038/nrc1045
- Hulbert A, Jusue-Torres I, Stark A, et al.: Early detection of lung cancer using DNA promoter hypermethylation in plasma and sputum. Clin Cancer Res. 2017, 23:1998-2005. 10.1158/1078-0432.CCR-16-1371
- Bailey VJ, Easwaran H, Zhang Y, et al.: MS-qFRET: a quantum dot-based method for analysis of DNA methylation. Genome Res. 2009, 19:1455-1461. 10.1101/gr.088831.108
- Li M, Chen WD, Papadopoulos N, et al.: Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol. 2009, 27:858-863. 10.1038/nbt.1559
- International Cancer Genome Consortium, Hudson TJ, Anderson W, et al.: International network of cancer genome projects. Nature. 2010, 443:993-998. 10.1038/nature08987
- Bernstein BE, Stamatoyannopoulos JA, Costello JF, et al.: The NIH Roadmap Epigenomics Mapping Consortium. Nat Biotechnol. 2010, 28:1045-1048. 10.1038/nbt1010-1045
- Garfield E: "Science Citation Index" - a new dimension in indexing. Science. 1964, 144:649-654. 10.1126/science.144.3619.649
- Gama-Sosa MA, Slagel VA, Trewyn RW, Oxenhandler R, Kuo KC, Gehrke CW, Ehrlich M: The 5-methylcytosine content of DNA from human tumors. Nucleic Acids Res. 1983, 11:6883-6894. 10.1093/nar/11.19.6883
1. Golub TR, Slonim DK, Tamayo P, et al.: Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science. 1999, 286:531-537. 10.1126/science.286.5439.531
2. Alizadeh AA, Eisen MB, Davis RE, et al.: Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000, 403:503-511. 10.1038/35000501
3. Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. P Natl Acad Scad USA. 1996, 93:9821-9826. 10.1073/pnas.93.18.9821
4. Barski A, Cuddapah S, Cui K, et al.: High-resolution profiling of histone methylations in the human genome. Cell. 2007, 129:823-837. 10.1016/j.cell.2007.05.009
5. Hegi ME, Diserens AC, Gorlia T, et al.: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005, 352:997-1003. 10.1056/NEJMoa043331
6. Cancer Genome Atlas Research Network: Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008, 455:1061-1068. 10.1038/nature07385
7. Cerami E, Gao J, Dogrusoz U, et al.: The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012, 2:401-404. 10.1158/2159-8290.CD-12-0095
8. Stupp R, Hegi ME, Mason WP, etal.: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009, 10:459-466. 10.1016/S1470-2045(09)70025-7
9. Cancer Genome Atlas Network: Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012, 487:330-337. 10.1038/nature11252
10. Verhaak RG, Hoadley KA, Purdom E, et al.: Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010, 17:98-110. 10.1016/j.ccr.2009.12.020
11. Cancer Genome Atlas Research Network: Integrated genomic analyses of ovarian carcinoma. Nature. 2011, 474:609-615. 10.1038/nature10166
12. Gupta RA, Shah N, Wang KC, et al.: Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010, 464:1071-1076. 10.1038/nature08975
13. Forner A, Llovet JM, Bruix J: Hepatocellular carcinoma. The Lancet. 2012, 379:1245-1255. 10.1016/s0140-6736(11)61347-0
14. Travis WD, Brambilla E, Noguchi M, et al.: International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011, 6:244-285. 10.1097/JTO.0b013e318206a221
15. Yanaihara N, Caplen N, Bowman E, et al.: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006, 9:189-198. 10.1016/j.ccr.2006.01.025
16. Curtis C, Shah SP, Chin SF, et al.: The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature. 2012, 486:346-352. 10.1038/nature10983
17. Neve RM, Chin K, Fridlyand J, et al.: A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 2006, 10:515-527. 10.1016/j.ccr.2006.10.008
18. Nielsen TO, Hsu FD, Jensen K, et al.: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004, 10:5367-5374. 10.1158/1078-0432.CCR-04-0220
19. Cancer Genome Atlas Research Network: Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012, 489:519-525. 10.1038/nature11404
20. Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP: CpG island methylator phenotype in colorectal cancer. P Natl Acad Scad USA. 1999, 96:8681-8686. 10.1073/pnas.96.15.8681
21. Takamizawa J, Konishi H, Yanagisawa K, et al.: Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004, 64:3753-3756. 10.1158/0008-5472.CAN-04-0637
22. Merlo A, Herman JG, Mao L, et al.: 5' CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med. 1995, 1:686-692. 10.1038/nm0795-686
23. Cancer Genome Atlas Research Network, Ley TJ, Miller C, et al.: Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013, 368:2059-2074. 10.1056/NEJMoa1301689
24. Varambally S, Dhanasekaran SM, Zhou M, et al.: The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002, 419:624-629. 10.1038/nature01075
25. Bhattacharjee A, Richards WG, Staunton J, et al.: Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. P Natl Acad Scad USA. 2001, 98:13790-13795. 10.1073/pnas.191502998
26. Esteller M, Corn PG, Baylin SB, Herman JG: A gene hypermethylation profile of human cancer. Cancer Res. 2001, 61:3225-3229.
27. Meissner A, Mikkelsen TS, Gu H, Wet al.: Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature. 2008, 454:766-770. 10.1038/nature07107
28. Zhang B, Pan X, Cobb GP, Anderson TA: microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007, 302:1-12. 10.1016/j.ydbio.2006.08.028
29. Kandoth C, McLellan MD, Vandin F, et al.: Mutational landscape and significance across 12 major cancer types. Nature. 2013, 502:333-339. 10.1038/nature12634
30. Cameron EE, Bachman KE, Myohanen S, Herman JG, Baylin SB: Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet. 1999, 21:103-107. 10.1038/5047
31. Clark SJ, Harrison J, Paul CL, Frommer M: High sensitivity mapping of methylated cytosines. Nucleic Acids Res. 1994, 22:2990-2997. 10.1093/nar/22.15.2990
32. Herman JG, Umar A, Polyak K, et al.: Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. P Natl Acad Scad USA. 1998, 95:6870-6875. 10.1073/pnas.95.12.6870
33. Cancer Genome Atlas Research Network: Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014, 513:202-209. 10.1038/nature13480
34. Cancer Genome Atlas Research Network: Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014, 511:543-550. 10.1038/nature13385
35. Brennan CW, Verhaak RG, McKenna A, et al.: The somatic genomic landscape of glioblastoma. Cell. 2013, 155:462-477. 10.1016/j.cell.2013.09.034
36. Esteller M, Garcia-Foncillas J, Andion E, et al.: Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 2000, 343:1350-1354. 10.1056/NEJM200011093431901
37. Cancer Genome Atlas Research Network, Weinstein JN, Collisson EA, et al.: The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet. 2013, 45:1113-1120. 10.1038/ng.2764
38. Weber M, Hellmann I, Stadler MB, Ramos L, Paabo S, Rebhan M, Schubeler D: Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet. 2007, 39:457-466. 10.1038/ng1990
39. Figueroa ME, Abdel-Wahab O, Lu C, et al.: Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010, 18:553-567. 10.1016/j.ccr.2010.11.015
40. Cancer Genome Atlas Research Network, Kandoth C, Schultz N, et al.: Integrated genomic characterization of endometrial carcinoma. Nature. 2013, 497:67-73. 10.1038/nature12113
41. Irizarry RA, Ladd-Acosta C, Wen B, et al.: The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet. 2009, 41:178-186. 10.1038/ng.298
42. Herman JG, Merlo A, Mao L, et al.: Inactivation of the Cdkn2/P16/Mts1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res. 1995, 55:4525-4530.
43. Narita M, Nunez S, Heard E, et al.: Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell. 2003, 113:703-716. 10.1016/s0092-8674(03)00401-x
44. Herman JG, Latif F, Weng Y, et al.: Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. P Natl Acad Scad USA. 1994, 91:9700-9704. 10.1073/pnas.91.21.9700
45. Swerdlow SH, Campo E, Pileri SA, et al.: The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016, 127:2375-2390. 10.1182/blood-2016-01-643569
46. Noushmehr H, Weisenberger DJ, Diefes K, et al.: Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010, 17:510-522. 10.1016/j.ccr.2010.03.017
47. Kane MF, Loda M, Gaida GM, et al.: Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res. 1997, 57:808-811.
48. Weisenberger DJ, Siegmund KD, Campan M, et al.: CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006, 38:787-793. 10.1038/ng1834
49. Weber M, Davies JJ, Wittig D, Oakeley EJ, Haase M, Lam WL, Schubeler D: Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet. 2005, 37:853-862. 10.1038/ng1598
50. Fraga MF, Ballestar E, Villar-Garea A, et al.: Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet. 2005, 37:391-400. 10.1038/ng1531
51. Fabbri M, Garzon R, Cimmino A, et al.: MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. P Natl Acad Scad USA. 2007, 104:15805-15810. 10.1073/pnas.0707628104
52. Orom UA, Derrien T, Beringer M, et al.: Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010, 143:46-58. 10.1016/j.cell.2010.09.001
53. Kleer CG, Cao Q, Varambally S, et al.: EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. P Natl Acad Scad USA. 2003, 100:11606-11611. 10.1073/pnas.1933744100
54. Cancer Genome Atlas Research Network: Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014, 507:315-322. 10.1038/nature12965
55. Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, Knippers R: DNA fragments in the blood plasma of cancer patients: Quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 2001, 61:1659-1665.
56. International Cancer Genome Consortium, Hudson TJ, Anderson W, et al.: International network of cancer genome projects. Nature. 2010, 464:993-998. 10.1038/nature08987
57. Costello JF, Fruhwald MC, Smiraglia DJ, et al.: Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet. 2000, 24:132-138. 10.1038/72785
58. Gaudet F, Hodgson JG, Eden A, et al.: Induction of tumors in mice by genomic hypomethylation. Science. 2003, 300:489-492. 10.1126/science.1083558
59. Sharma SV, Lee DY, Li B, et al.: A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell. 2010, 141:69-80. 10.1016/j.cell.2010.02.027
60. Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG: Inactivation of the DNA repair gene O-6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res. 1999, 59:793-797.
61. Zuber J, Shi J, Wang E, et al.: RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature. 2011, 478:524-528. 10.1038/nature10334
62. Iorio MV, Visone R, Di Leva G, et al.: MicroRNA signatures in human ovarian cancer. Cancer Res. 2007, 67:8699-8707. 10.1158/0008-5472.CAN-07-1936
63. Dweep H, Sticht C, Pandey P, Gretz N: miRWalk--database: prediction of possible miRNA binding sites by "walking" the genes of three genomes. J Biomed Inform. 2011, 44:839-847. 10.1016/j.jbi.2011.05.002
64. Comijn J, Berx G, Vermassen P, et al.: The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell. 2001, 7:1267-1278. 10.1016/s1097-2765(01)00260-x
65. Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB: Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet. 1994, 7:536-540. 10.1038/ng0894-536
66. Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T: Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem. 2010, 285:17442-17452. 10.1074/jbc.M110.107821
67. Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA, Jones PA: Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell. 2006, 9:435-443. 10.1016/j.ccr.2006.04.020
68. Carroll JS, Meyer CA, Song J, et al.: Genome-wide analysis of estrogen receptor binding sites. Nat Genet. 2006, 38:1289-1297. 10.1038/ng1901
69. Valk PJ, Verhaak RG, Beijen MA, et al.: Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med. 2004, 350:1617-1628. 10.1056/NEJMoa040465
70. Weinstein JN, Myers TG, O'Connor PM, et al.: An information-intensive approach to the molecular pharmacology of cancer. Science. 1997, 275:343-349. 10.1126/science.275.5298.343
71. Kantarjian H, Issa JP, Rosenfeld CS, et al.: Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006, 106:1794-1803. 10.1002/cncr.21792
72. Houseman EA, Accomando WP, Koestler DC, et al.: DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinform. 2012, 13:86. 10.1186/1471-2105-13-86
73. Patel AP, Tirosh I, Trombetta JJ, et al.: Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014, 344:1396-1401. 10.1126/science.1254257
74. West M, Blanchette C, Dressman H, et al.: Predicting the clinical status of human breast cancer by using gene expression profiles. P Natl Acad Scad USA. 2001, 98:11462-11467. 10.1073/pnas.201162998
75. Turchinovich A, Weiz L, Langheinz A, Burwinkel B: Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011, 39:7223-7233. 10.1093/nar/gkr254
76. McCabe MT, Ott HM, Ganji G, et al.: EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 2012, 492:108-112. 10.1038/nature11606
77. Dammann R, Li C, Yoon JH, Chin PL, Bates S, Pfeifer GP: Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet. 2000, 25:315-319. 10.1038/77083
78. Turcan S, Rohle D, Goenka A, et al.: IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature. 2012, 483:479-483. 10.1038/nature10866
79. Rhee I, Bachman KE, Park BH, et al.: DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature. 2002, 416:552-556. 10.1038/416552a
80. Lapointe J, Li C, Higgins JP, et al.: Gene expression profiling identifies clinically relevant subtypes of prostate cancer. P Natl Acad Scad USA. 2004, 101:811-816. 10.1073/pnas.0304146101
81. Eckhardt F, Lewin J, Cortese R, et al.: DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet. 2006, 38:1378-1385. 10.1038/ng1909
82. Bos PD, Zhang XH, Nadal C, et al.: Genes that mediate breast cancer metastasis to the brain. Nature. 2009, 459:1005-1009. 10.1038/nature08021
83. Iliopoulos D, Hirsch HA, Struhl K: An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell. 2009, 139:693-706. 10.1016/j.cell.2009.10.014
84. Bracken AP, Dietrich N, Pasini D, Hansen KH, Helin K: Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev. 2006, 20:1123-1136. 10.1101/gad.381706
85. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES: The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011, 117:5019-5032. 10.1182/blood-2011-01-293050
86. Chapman MA, Lawrence MS, Keats JJ, et al.: Initial genome sequencing and analysis of multiple myeloma. Nature. 2011, 471:467-472. 10.1038/nature09837
87. Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, Shimotohno K: Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene. 2006, 25:2537-2545. 10.1038/sj.onc.1209283
88. Gregoretti IV, Lee YM, Goodson HV: Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol. 2004, 338:17-31. 10.1016/j.jmb.2004.02.006
89. Li QL, Ito K, Sakakura C, et al.: Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell. 2002, 109:113-124. 10.1016/S0092-8674(02)00690-6
90. Ng EK, Chong WW, Jin H, et al.: Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut. 2009, 58:1375-1381. 10.1136/gut.2008.167817
91. Bibikova M, Barnes B, Tsan C, et al.: High density DNA methylation array with single CpG site resolution. Genomics. 2011, 98:288-295. 10.1016/j.ygeno.2011.07.007
92. Yap KL, Li S, Munoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, Gil J, Walsh MJ, Zhou MM: Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell. 2010, 38:662-674. 10.1016/j.molcel.2010.03.021
93. Suzuki H, Watkins DN, Jair KW, et al.: Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet. 2004, 36:417-422. 10.1038/ng1330
94. Esteller M, Silva JM, Dominguez G, et al.: Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst. 2000, 92:564-569. 10.1093/jnci/92.7.564
95. Schlesinger Y, Straussman R, Keshet I, et al.: Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat Genet. 2007, 39:232-236. 10.1038/ng1950
96. Shimono Y, Zabala M, Cho RW, et al.: Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell. 2009, 138:592-603. 10.1016/j.cell.2009.07.011
97. Doi A, Park IH, Wen B, et al.: Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nat Genet. 2009, 41:1350-1353. 10.1038/ng.471
98. Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, Herman JG: Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res. 1999, 59:67-70.
99. Belinsky SA, Nikula KJ, Palmisano WA, et al.: Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. P Natl Acad Scad USA. 1998, 95:11891-11896. 10.1073/pnas.95.20.11891
100. Rainier S, Johnson LA, Dobry CJ, Ping AJ, Grundy PE, Feinberg AP: Relaxation of imprinted genes in human cancer. Nature. 1993, 362:747-749. 10.1038/362747a0
The 100 Most Cited Papers About Cancer Epigenetics
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Cite this article as:
Jusue-Torres I, Mendoza J E, Brock M V, et al. (April 10, 2020) The 100 Most Cited Papers About Cancer Epigenetics. Cureus 12(4): e7623. doi:10.7759/cureus.7623
Received by Cureus: March 20, 2020
Peer review began: April 01, 2020
Peer review concluded: April 03, 2020
Published: April 10, 2020
© Copyright 2020
Jusue-Torres et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.