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Published in: Surgery Today 12/2017

01-12-2017 | Original Article

LINE-1 methylation level and prognosis in pancreas cancer: pyrosequencing technology and literature review

Authors: Kensuke Yamamura, Keisuke Kosumi, Yoshifumi Baba, Kazuto Harada, Feng Gao, Xiaobo Zhang, Lei Zhou, Yuki Kitano, Kota Arima, Takayoshi Kaida, Hideaki Takeyama, Takaaki Higashi, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Xiaodong Tan, Hideo Baba

Published in: Surgery Today | Issue 12/2017

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Abstract

Purpose

Global DNA hypomethylation plays an important role in genomic instability and carcinogenesis. The long interspersed nucleotide element-1 (LINE-1) methylation level is a good surrogate marker of the global DNA methylation level. Previously, we demonstrated a strong relationship between LINE-1 hypomethylation and poor prognosis in certain cancers. However, the relationship between the LINE-1 methylation level and the clinical outcome of pancreatic cancer (PC) remains unclear.

Methods

We used a pyrosequencing assay to measure LINE-1 methylation levels in 126 samples of resected PC and evaluated the prognostic value of the LINE-1 methylation level.

Results

LINE-1 methylation levels were significantly lower in PC tissues than in matched noncancerous pancreatic tissues (p = 0.039, n = 36). The tumoral LINE-1 methylation range was 41.3–92.8 (n = 126, mean 77.7, median 78.5, standard deviation 5.7). The LINE-1 methylation level was unrelated to clinical and pathological features. Moreover, LINE-1 hypomethylation was not significantly associated with overall survival, cancer specific survival, or disease-free survival (log-rank p = 0.30, p = 0.18 and p = 0.50, respectively).

Conclusion

The LINE-1 methylation level appears not to be associated with poor prognosis in PC. The effect of the LINE-1 methylation level on the survival of PC patients needs to be confirmed in a larger-cohort study.
Literature
1.
2.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
3.
go back to reference Garcea G, Dennison AR, Pattenden CJ, Neal CP, Sutton CD, Berry DP. Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature. JOP. 2008;9:99–132.PubMed Garcea G, Dennison AR, Pattenden CJ, Neal CP, Sutton CD, Berry DP. Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature. JOP. 2008;9:99–132.PubMed
4.
go back to reference Fukuda Y, Yamada D, Eguchi H, Iwagami Y, Noda T, Asaoka T, et al. A novel preoperative predictor of pancreatic fistula using computed tomography after distal pancreatectomy with staple closure. Surg Today. 2017. doi:10.1007/S00595-017-1495-9. Fukuda Y, Yamada D, Eguchi H, Iwagami Y, Noda T, Asaoka T, et al. A novel preoperative predictor of pancreatic fistula using computed tomography after distal pancreatectomy with staple closure. Surg Today. 2017. doi:10.​1007/​S00595-017-1495-9.
5.
go back to reference Katayama H, Kurokawa Y, Nakamura K, Ito H, Kanemitsu Y, Masuda N, et al. Extended Clavien–Dindo classification of surgical complications: Japan Clinical Oncology Group postoperative complications criteria. Surg Today. 2016;46:668–85.CrossRefPubMed Katayama H, Kurokawa Y, Nakamura K, Ito H, Kanemitsu Y, Masuda N, et al. Extended Clavien–Dindo classification of surgical complications: Japan Clinical Oncology Group postoperative complications criteria. Surg Today. 2016;46:668–85.CrossRefPubMed
6.
go back to reference Rodriguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology. Nat Med. 2011;17:330–9.CrossRefPubMed Rodriguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology. Nat Med. 2011;17:330–9.CrossRefPubMed
9.
go back to reference Berman BP, Weisenberger DJ, Aman JF, Hinoue T, Ramjan Z, Liu Y, et al. Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Nat Genet. 2012;44:40–6.CrossRef Berman BP, Weisenberger DJ, Aman JF, Hinoue T, Ramjan Z, Liu Y, et al. Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Nat Genet. 2012;44:40–6.CrossRef
10.
go back to reference Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, Gray JW, et al. Induction of tumors in mice by genomic hypomethylation. Science. 2003;300:489–92.CrossRefPubMed Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, Gray JW, et al. Induction of tumors in mice by genomic hypomethylation. Science. 2003;300:489–92.CrossRefPubMed
11.
go back to reference Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002;3:415–28.CrossRefPubMed Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002;3:415–28.CrossRefPubMed
13.
go back to reference Irahara N, Nosho K, Baba Y, Shima K, Lindeman NI, Hazra A, et al. Precision of pyrosequencing assay to measure LINE-1 methylation in colon cancer, normal colonic mucosa, and peripheral blood cells. J Mol Diagn. 2010;12:177–83.CrossRefPubMedPubMedCentral Irahara N, Nosho K, Baba Y, Shima K, Lindeman NI, Hazra A, et al. Precision of pyrosequencing assay to measure LINE-1 methylation in colon cancer, normal colonic mucosa, and peripheral blood cells. J Mol Diagn. 2010;12:177–83.CrossRefPubMedPubMedCentral
14.
go back to reference Ogino S, Kawasaki T, Nosho K, Ohnishi M, Suemoto Y, Kirkner GJ, et al. LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer. Int J Cancer. 2008;122:2767–73.CrossRefPubMedPubMedCentral Ogino S, Kawasaki T, Nosho K, Ohnishi M, Suemoto Y, Kirkner GJ, et al. LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer. Int J Cancer. 2008;122:2767–73.CrossRefPubMedPubMedCentral
15.
go back to reference Yang AS, Estecio MR, Doshi K, Kondo Y, Tajara EH, Issa JP. A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic Acids Res. 2004;32:e38.CrossRefPubMedPubMedCentral Yang AS, Estecio MR, Doshi K, Kondo Y, Tajara EH, Issa JP. A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic Acids Res. 2004;32:e38.CrossRefPubMedPubMedCentral
16.
go back to reference Ahn JB, Chung WB, Maeda O, Shin SJ, Kim HS, Chung HC, et al. DNA methylation predicts recurrence from resected stage III proximal colon cancer. Cancer. 2011;117:1847–54.CrossRefPubMed Ahn JB, Chung WB, Maeda O, Shin SJ, Kim HS, Chung HC, et al. DNA methylation predicts recurrence from resected stage III proximal colon cancer. Cancer. 2011;117:1847–54.CrossRefPubMed
17.
go back to reference Compton CC, Byrd DR, Garcia-Aguilar J, Kurtzman SH, Olawaiye A, Washington MK. The AJCC Cancer Staging Atlas. 2nd ed. Berlin: Springer; 2012.CrossRef Compton CC, Byrd DR, Garcia-Aguilar J, Kurtzman SH, Olawaiye A, Washington MK. The AJCC Cancer Staging Atlas. 2nd ed. Berlin: Springer; 2012.CrossRef
18.
go back to reference McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, et al. Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst. 2005;97:1180–4.CrossRefPubMed McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, et al. Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst. 2005;97:1180–4.CrossRefPubMed
19.
go back to reference Ogino S, Nosho K, Kirkner GJ, Kawasaki T, Chan AT, Schernhammer ES, et al. A cohort study of tumoral LINE-1 hypomethylation and prognosis in colon cancer. J Natl Cancer Inst. 2008;100:1734–8.CrossRefPubMedPubMedCentral Ogino S, Nosho K, Kirkner GJ, Kawasaki T, Chan AT, Schernhammer ES, et al. A cohort study of tumoral LINE-1 hypomethylation and prognosis in colon cancer. J Natl Cancer Inst. 2008;100:1734–8.CrossRefPubMedPubMedCentral
20.
go back to reference Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ishimoto T, et al. LINE-1 hypomethylation is associated with a poor prognosis among patients with curatively resected esophageal squamous cell carcinoma. Ann Surg. 2013;257:449–55.CrossRefPubMed Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ishimoto T, et al. LINE-1 hypomethylation is associated with a poor prognosis among patients with curatively resected esophageal squamous cell carcinoma. Ann Surg. 2013;257:449–55.CrossRefPubMed
21.
go back to reference Shigaki H, Baba Y, Watanabe M, Murata A, Iwagami S, Miyake K, et al. LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis. Gastric Cancer. 2013;16:480–7.CrossRefPubMed Shigaki H, Baba Y, Watanabe M, Murata A, Iwagami S, Miyake K, et al. LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis. Gastric Cancer. 2013;16:480–7.CrossRefPubMed
22.
go back to reference Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ida S, et al. Pyrosequencing assay to measure LINE-1 methylation level in esophageal squamous cell carcinoma. Ann Surg Oncol. 2012;19:2726–32.CrossRefPubMed Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ida S, et al. Pyrosequencing assay to measure LINE-1 methylation level in esophageal squamous cell carcinoma. Ann Surg Oncol. 2012;19:2726–32.CrossRefPubMed
23.
go back to reference Baba Y, Huttenhower C, Nosho K, Tanaka N, Shima K, Hazra A, et al. Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors. Mol Cancer. 2010;9:125.CrossRefPubMedPubMedCentral Baba Y, Huttenhower C, Nosho K, Tanaka N, Shima K, Hazra A, et al. Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors. Mol Cancer. 2010;9:125.CrossRefPubMedPubMedCentral
24.
go back to reference Pattamadilok J, Huapai N, Rattanatanyong P, Vasurattana A, Triratanachat S, Tresukosol D, et al. LINE-1 hypomethylation level as a potential prognostic factor for epithelial ovarian cancer. Int J Gynecol Cancer. 2008;18:711–7.CrossRefPubMed Pattamadilok J, Huapai N, Rattanatanyong P, Vasurattana A, Triratanachat S, Tresukosol D, et al. LINE-1 hypomethylation level as a potential prognostic factor for epithelial ovarian cancer. Int J Gynecol Cancer. 2008;18:711–7.CrossRefPubMed
25.
go back to reference Harada K, Baba Y, Ishimoto T, Chikamoto A, Kosumi K, Hayashi H, et al. LINE-1 methylation level and patient prognosis in a database of 208 hepatocellular carcinomas. Ann Surg Oncol. 2015;22:1280–7.CrossRefPubMed Harada K, Baba Y, Ishimoto T, Chikamoto A, Kosumi K, Hayashi H, et al. LINE-1 methylation level and patient prognosis in a database of 208 hepatocellular carcinomas. Ann Surg Oncol. 2015;22:1280–7.CrossRefPubMed
26.
go back to reference Tomihara H, Eguchi H, Yamada D, Gotoh K, Kawamoto K, Wada H, et al. Preoperative chemoradiotherapy does not compromise the feasibility of adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma. Surg Today. 2017;47:218–26.CrossRefPubMed Tomihara H, Eguchi H, Yamada D, Gotoh K, Kawamoto K, Wada H, et al. Preoperative chemoradiotherapy does not compromise the feasibility of adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma. Surg Today. 2017;47:218–26.CrossRefPubMed
27.
go back to reference Ohka F, Natsume A, Motomura K, Kishida Y, Kondo Y, Abe T, et al. The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma. PLoS One. 2011;6:e23332.CrossRefPubMedPubMedCentral Ohka F, Natsume A, Motomura K, Kishida Y, Kondo Y, Abe T, et al. The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma. PLoS One. 2011;6:e23332.CrossRefPubMedPubMedCentral
28.
go back to reference Roman-Gomez J, Jimenez-Velasco A, Agirre X, Cervantes F, Sanchez J, Garate L, et al. Promoter hypomethylation of the LINE-1 retrotransposable elements activates sense/antisense transcription and marks the progression of chronic myeloid leukemia. Oncogene. 2005;24:7213–23.CrossRefPubMed Roman-Gomez J, Jimenez-Velasco A, Agirre X, Cervantes F, Sanchez J, Garate L, et al. Promoter hypomethylation of the LINE-1 retrotransposable elements activates sense/antisense transcription and marks the progression of chronic myeloid leukemia. Oncogene. 2005;24:7213–23.CrossRefPubMed
29.
go back to reference Saito K, Kawakami K, Matsumoto I, Oda M, Watanabe G, Minamoto T. Long interspersed nuclear element 1 hypomethylation is a marker of poor prognosis in stage IA non-small cell lung cancer. Clin Cancer Res. 2010;16:2418–26.CrossRefPubMed Saito K, Kawakami K, Matsumoto I, Oda M, Watanabe G, Minamoto T. Long interspersed nuclear element 1 hypomethylation is a marker of poor prognosis in stage IA non-small cell lung cancer. Clin Cancer Res. 2010;16:2418–26.CrossRefPubMed
30.
go back to reference Sigalotti L, Fratta E, Bidoli E, Covre A, Parisi G, Colizzi F, et al. Methylation levels of the “long interspersed nucleotide element-1” repetitive sequences predict survival of melanoma patients. J Transl Med. 2011;9:78.CrossRefPubMedPubMedCentral Sigalotti L, Fratta E, Bidoli E, Covre A, Parisi G, Colizzi F, et al. Methylation levels of the “long interspersed nucleotide element-1” repetitive sequences predict survival of melanoma patients. J Transl Med. 2011;9:78.CrossRefPubMedPubMedCentral
31.
go back to reference Holm TM, Jackson-Grusby L, Brambrink T, Yamada Y, Rideout WM 3rd, Jaenisch R. Global loss of imprinting leads to widespread tumorigenesis in adult mice. Cancer Cell. 2005;8:275–85.CrossRefPubMed Holm TM, Jackson-Grusby L, Brambrink T, Yamada Y, Rideout WM 3rd, Jaenisch R. Global loss of imprinting leads to widespread tumorigenesis in adult mice. Cancer Cell. 2005;8:275–85.CrossRefPubMed
32.
go back to reference Suzuki K, Suzuki I, Leodolter A, Alonso S, Horiuchi S, Yamashita K, et al. Global DNA demethylation in gastrointestinal cancer is age dependent and precedes genomic damage. Cancer Cell. 2006;9:199–207.CrossRefPubMed Suzuki K, Suzuki I, Leodolter A, Alonso S, Horiuchi S, Yamashita K, et al. Global DNA demethylation in gastrointestinal cancer is age dependent and precedes genomic damage. Cancer Cell. 2006;9:199–207.CrossRefPubMed
33.
go back to reference Karpf AR, Matsui S. Genetic disruption of cytosine DNA methyltransferase enzymes induces chromosomal instability in human cancer cells. Cancer Res. 2005;65:8635–9.CrossRefPubMed Karpf AR, Matsui S. Genetic disruption of cytosine DNA methyltransferase enzymes induces chromosomal instability in human cancer cells. Cancer Res. 2005;65:8635–9.CrossRefPubMed
34.
go back to reference Shahrzad S, Bertrand K, Minhas K, Coomber BL. Induction of DNA hypomethylation by tumor hypoxia. Epigenetics. 2007;2:119–25.CrossRefPubMed Shahrzad S, Bertrand K, Minhas K, Coomber BL. Induction of DNA hypomethylation by tumor hypoxia. Epigenetics. 2007;2:119–25.CrossRefPubMed
36.
go back to reference Peaston AE, Evsikov AV, Graber JH, de Vries WN, Holbrook AE, Solter D, et al. Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Dev Cell. 2004;7:597–606.CrossRefPubMed Peaston AE, Evsikov AV, Graber JH, de Vries WN, Holbrook AE, Solter D, et al. Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Dev Cell. 2004;7:597–606.CrossRefPubMed
37.
go back to reference Faulkner GJ, Kimura Y, Daub CO, Wani S, Plessy C, Irvine KM, et al. The regulated retrotransposon transcriptome of mammalian cells. Nat Genet. 2009;41:563–71.CrossRefPubMed Faulkner GJ, Kimura Y, Daub CO, Wani S, Plessy C, Irvine KM, et al. The regulated retrotransposon transcriptome of mammalian cells. Nat Genet. 2009;41:563–71.CrossRefPubMed
38.
go back to reference Sato N, Fukushima N, Maitra A, Matsubayashi H, Yeo CJ, Cameron JL, et al. Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays. Cancer Res. 2003;63:3735–42.PubMed Sato N, Fukushima N, Maitra A, Matsubayashi H, Yeo CJ, Cameron JL, et al. Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays. Cancer Res. 2003;63:3735–42.PubMed
39.
go back to reference Goto Y, Zeng L, Yeom CJ, Zhu Y, Morinibu A, Shinomiya K, et al. UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1alpha. Nat Commun. 2015;6:6153.CrossRefPubMedPubMedCentral Goto Y, Zeng L, Yeom CJ, Zhu Y, Morinibu A, Shinomiya K, et al. UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1alpha. Nat Commun. 2015;6:6153.CrossRefPubMedPubMedCentral
40.
go back to reference Wada M, Yazumi S, Takaishi S, Hasegawa K, Sawada M, Tanaka H, et al. Frequent loss of RUNX3 gene expression in human bile duct and pancreatic cancer cell lines. Oncogene. 2004;23:2401–7.CrossRefPubMed Wada M, Yazumi S, Takaishi S, Hasegawa K, Sawada M, Tanaka H, et al. Frequent loss of RUNX3 gene expression in human bile duct and pancreatic cancer cell lines. Oncogene. 2004;23:2401–7.CrossRefPubMed
41.
go back to reference Nomoto S, Kinoshita T, Mori T, Kato K, Sugimoto H, Kanazumi N, et al. Adverse prognosis of epigenetic inactivation in RUNX3 gene at 1p36 in human pancreatic cancer. Br J Cancer. 2008;98:1690–5.CrossRefPubMedPubMedCentral Nomoto S, Kinoshita T, Mori T, Kato K, Sugimoto H, Kanazumi N, et al. Adverse prognosis of epigenetic inactivation in RUNX3 gene at 1p36 in human pancreatic cancer. Br J Cancer. 2008;98:1690–5.CrossRefPubMedPubMedCentral
42.
go back to reference Rodic N, Steranka JP, Makohon-Moore A, Moyer A, Shen P, Sharma R, et al. Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma. Nat Med. 2015;21:1060–4.CrossRefPubMedPubMedCentral Rodic N, Steranka JP, Makohon-Moore A, Moyer A, Shen P, Sharma R, et al. Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma. Nat Med. 2015;21:1060–4.CrossRefPubMedPubMedCentral
43.
go back to reference Rodic N, Sharma R, Sharma R, Zampella J, Dai L, Taylor MS, et al. Long interspersed element-1 protein expression is a hallmark of many human cancers. Am J Pathol. 2014;184:1280–6.CrossRefPubMedPubMedCentral Rodic N, Sharma R, Sharma R, Zampella J, Dai L, Taylor MS, et al. Long interspersed element-1 protein expression is a hallmark of many human cancers. Am J Pathol. 2014;184:1280–6.CrossRefPubMedPubMedCentral
44.
go back to reference Kawano H, Saeki H, Kitao H, Tsuda Y, Otsu H, Ando K, Ito S, Egashira A, Oki E, Morita M, Oda Y, Maehara Y. Chromosomal instability associated with global DNA hypomethylation is associated with the initiation and progression of esophageal squamous cell carcinoma. Ann Surg Oncol. 2014;21(S4):696–702.CrossRef Kawano H, Saeki H, Kitao H, Tsuda Y, Otsu H, Ando K, Ito S, Egashira A, Oki E, Morita M, Oda Y, Maehara Y. Chromosomal instability associated with global DNA hypomethylation is associated with the initiation and progression of esophageal squamous cell carcinoma. Ann Surg Oncol. 2014;21(S4):696–702.CrossRef
45.
go back to reference Bae JM, Shin SH, Kwon HJ, Park SY, Kook MC, Kim YW, Cho NY, Kim N, Kim TY, Kim D, Kang GH. ALU and LINE-1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications. Int J Cancer. 2012;131(6):1323–31.CrossRefPubMed Bae JM, Shin SH, Kwon HJ, Park SY, Kook MC, Kim YW, Cho NY, Kim N, Kim TY, Kim D, Kang GH. ALU and LINE-1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications. Int J Cancer. 2012;131(6):1323–31.CrossRefPubMed
46.
go back to reference Antelo M, Balaguer F, Shia J, Shen Y, Hur K, Moreira L, Cuatrecasas M, Bujanda L, Giraldez MD, Takahashi M, Cabanne A, Barugel ME, Arnold M, Roca EL, Andreu M, Castellvi-Bel S, Llor X, Jover R, Castells A, Boland CR, Goel A, Lo AWI. A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer. PLoS One. 2012;7(9):e45357.CrossRefPubMedPubMedCentral Antelo M, Balaguer F, Shia J, Shen Y, Hur K, Moreira L, Cuatrecasas M, Bujanda L, Giraldez MD, Takahashi M, Cabanne A, Barugel ME, Arnold M, Roca EL, Andreu M, Castellvi-Bel S, Llor X, Jover R, Castells A, Boland CR, Goel A, Lo AWI. A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer. PLoS One. 2012;7(9):e45357.CrossRefPubMedPubMedCentral
47.
go back to reference Rhee YY, Kim MJ, Bae JM, Koh JM, Cho NY, Juhnn YS, Kim D, Kang GH. Clinical outcomes of patients with microsatellite-unstable colorectal carcinomas depend on L1 methylation level. Ann Surg Oncol. 2012;19(11):3441–8CrossRefPubMed Rhee YY, Kim MJ, Bae JM, Koh JM, Cho NY, Juhnn YS, Kim D, Kang GH. Clinical outcomes of patients with microsatellite-unstable colorectal carcinomas depend on L1 methylation level. Ann Surg Oncol. 2012;19(11):3441–8CrossRefPubMed
48.
go back to reference Hoshimoto S, Kuo CT, Chong KK, Takeshima TL, Takei Y, Li MW, Huang SK, Sim MS, Morton DL, Hoon DS. AIM1 and LINE-1 epigenetic aberrations in tumor and serum relate to melanoma progression and disease outcome. J Invest Dermatol. 2012;132(6):1689–97.CrossRefPubMedPubMedCentral Hoshimoto S, Kuo CT, Chong KK, Takeshima TL, Takei Y, Li MW, Huang SK, Sim MS, Morton DL, Hoon DS. AIM1 and LINE-1 epigenetic aberrations in tumor and serum relate to melanoma progression and disease outcome. J Invest Dermatol. 2012;132(6):1689–97.CrossRefPubMedPubMedCentral
49.
go back to reference van Hoesel AQ, van de Velde CJ, Kuppen PJ, Liefers GJ, Putter H, Sato Y, Elashoff DA, Turner RR, Shamonki JM, de Kruijf EM, van Nes JG, Giuliano AE, Hoon DS. Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study. Breast Cancer Res Treat. 2012;134(3):1103–14. van Hoesel AQ, van de Velde CJ, Kuppen PJ, Liefers GJ, Putter H, Sato Y, Elashoff DA, Turner RR, Shamonki JM, de Kruijf EM, van Nes JG, Giuliano AE, Hoon DS. Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study. Breast Cancer Res Treat. 2012;134(3):1103–14.
50.
go back to reference Aoki Y, Nojima M, Suzuki H, Yasui H, Maruyama R, Yamamoto E, Ashida M, Itagaki M, Asaoku H, Ikeda H, Hayashi T, Imai K, Mori M, Tokino T, Ishida T, Toyota M, Shinomura Y. Genomic vulnerability to LINE-1 hypomethylation is a potential determinant of the clinicogenetic features of multiple myeloma. Genome Med. 2012;4(12):101.CrossRefPubMedPubMedCentral Aoki Y, Nojima M, Suzuki H, Yasui H, Maruyama R, Yamamoto E, Ashida M, Itagaki M, Asaoku H, Ikeda H, Hayashi T, Imai K, Mori M, Tokino T, Ishida T, Toyota M, Shinomura Y. Genomic vulnerability to LINE-1 hypomethylation is a potential determinant of the clinicogenetic features of multiple myeloma. Genome Med. 2012;4(12):101.CrossRefPubMedPubMedCentral
Metadata
Title
LINE-1 methylation level and prognosis in pancreas cancer: pyrosequencing technology and literature review
Authors
Kensuke Yamamura
Keisuke Kosumi
Yoshifumi Baba
Kazuto Harada
Feng Gao
Xiaobo Zhang
Lei Zhou
Yuki Kitano
Kota Arima
Takayoshi Kaida
Hideaki Takeyama
Takaaki Higashi
Katsunori Imai
Daisuke Hashimoto
Akira Chikamoto
Xiaodong Tan
Hideo Baba
Publication date
01-12-2017
Publisher
Springer Japan
Published in
Surgery Today / Issue 12/2017
Print ISSN: 0941-1291
Electronic ISSN: 1436-2813
DOI
https://doi.org/10.1007/s00595-017-1539-1

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