Chromosome 7 gain and DNA hypermethylation at the HOXA10 locus are associated with expression of a stem cell related HOX-signature in glioblastoma
详细信息 查看全文
- 作者：Sebastian Kurscheid (1) (16) (2) (3)
Pierre Bady (1) (2) (3) (4)
Davide Sciuscio (1) (2)
Ivana Samarzija (1) (2)
Tal Shay (5)
Irene Vassallo (1) (2)
Wim V Criekinge (6)
Roy T Daniel (1)
Martin J van den Bent (7)
Christine Marosi (8)
Michael Weller (10) (9)
Warren P Mason (11)
Eytan Domany (12)
Roger Stupp (1) (13)
Mauro Delorenzi (14) (15) (3)
Monika E Hegi (1) (2)
1. Neurosurgery ; Lausanne University Hospital ; Lausanne ; 1011 ; Switzerland
16. Present address ; The John Curtin School of Medical Research ; The Australian National University ; Canberra ; ACT 2601 ; Australia
2. Neuroscience Research Center ; Lausanne University Hospital ; Lausanne ; 1011 ; Switzerland
3. Bioinformatics Core Facility ; Swiss Institute for Bioinformatics ; Lausanne ; 1005 ; Switzerland
4. Department of Education and Research ; University of Lausanne ; Lausanne ; 1011 ; Switzerland
5. Ben-Gurion University of the Negev ; Beersheba ; Israel
6. Department of Mathematical Modelling ; Statistics and Bioinformatics ; Ghent University ; Ghent ; Belgium
7. Department of Neurology/Neurooncology ; Erasmus MC Cancer Center ; Rotterdam ; The Netherlands
8. Department of Medicine ; Medical University Vienna ; Vienna ; Austria
10. Department of Neurology ; University Hospital Zurich ; Zurich ; Switzerland
9. Department of Neurology ; University of T眉bingen ; T眉bingen ; Germany
11. Princess Margaret Hospital ; University of Toronto ; Toronto ; Canada
12. Department of Physics of Complex Systems ; Weizmann Institute of Science ; Rehovot ; Israel
13. Department of Oncology ; University Hospital Zurich ; Zurich ; 8091 ; Switzerland
14. Ludwig Center for Cancer Research ; University of Lausanne ; Lausanne ; 1011 ; Switzerland
15. Department of Oncology ; University of Lausanne ; Lausanne ; 1011 ; Switzerland - 刊名：Genome Biology
- 出版年：2015
- 出版时间：December 2015
- 年：2015
- 卷：16
- 期：1
- 全文大小：2,551 KB
- 参考文献：1. Weller, M, Pfister, SM, Wick, W, Hegi, ME, Reifenberger, G, Stupp, R (2013) Molecular neuro-oncology in clinical practice: a new horizon. Lancet Oncol 14: pp. e370-9 ternal" href="http://dx.doi.org/10.1016/S1470-2045(13)70168-2" target="_blank" title="It opens in new window">CrossRef
2. Brennan, CW, Verhaak, RG, McKenna, A, Campos, B, Noushmehr, H, Salama, SR (2013) The somatic genomic landscape of glioblastoma. Cell 155: pp. 462-77 ternal" href="http://dx.doi.org/10.1016/j.cell.2013.09.034" target="_blank" title="It opens in new window">CrossRef
3. Sottoriva, A, Spiteri, I, Piccirillo, SG, Touloumis, A, Collins, VP, Marioni, JC (2013) Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci U S A 110: pp. 4009-14 ternal" href="http://dx.doi.org/10.1073/pnas.1219747110" target="_blank" title="It opens in new window">CrossRef
4. Singh, SK, Hawkins, C, Clarke, ID, Squire, JA, Bayani, J, Hide, T (2004) Identification of human brain tumour initiating cells. Nature 432: pp. 396-401 ternal" href="http://dx.doi.org/10.1038/nature03128" target="_blank" title="It opens in new window">CrossRef
5. Bao, S, Wu, Q, McLendon, RE, Hao, Y, Shi, Q, Hjelmeland, AB (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444: pp. 756-60 ternal" href="http://dx.doi.org/10.1038/nature05236" target="_blank" title="It opens in new window">CrossRef
6. Chen, J, Li, Y, Yu, TS, McKay, RM, Burns, DK, Kernie, SG (2012) A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488: pp. 522-6 ternal" href="http://dx.doi.org/10.1038/nature11287" target="_blank" title="It opens in new window">CrossRef
7. Murat, A, Migliavacca, E, Gorlia, T, Lambiv, WL, Shay, T, Hamou, MF (2008) Stem cell-related 鈥渟elf-renewal鈥?signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol 26: pp. 3015-24 ternal" href="http://dx.doi.org/10.1200/JCO.2007.15.7164" target="_blank" title="It opens in new window">CrossRef
8. Gallo, M, Ho, J, Coutinho, F, Vanner, R, Lee, L, Head, R (2012) A tumorigenic MLL-homeobox network in human glioblastoma stem cells. Cancer Res 73: pp. 417-27 ternal" href="http://dx.doi.org/10.1158/0008-5472.CAN-12-1881" target="_blank" title="It opens in new window">CrossRef
9. Abdel-Fattah, R, Xiao, A, Bomgardner, D, Pease, CS, Lopes, MB, Hussaini, IM (2006) Differential expression of HOX genes in neoplastic and non-neoplastic human astrocytes. J Pathol 209: pp. 15-24 ternal" href="http://dx.doi.org/10.1002/path.1939" target="_blank" title="It opens in new window">CrossRef
10. Costa, BM, Smith, JS, Chen, Y, Chen, J, Phillips, HS, Aldape, KD (2010) Reversing HOXA9 oncogene activation by PI3K inhibition: epigenetic mechanism and prognostic significance in human glioblastoma. Cancer Res 70: pp. 453-62 ternal" href="http://dx.doi.org/10.1158/0008-5472.CAN-09-2189" target="_blank" title="It opens in new window">CrossRef
11. Gaspar, N, Marshall, L, Perryman, L, Bax, DA, Little, SE, Viana-Pereira, M (2010) MGMT-independent temozolomide resistance in pediatric glioblastoma cells associated with a PI3-kinase-mediated HOX/stem cell gene signature. Cancer Res 70: pp. 9243-52 ternal" href="http://dx.doi.org/10.1158/0008-5472.CAN-10-1250" target="_blank" title="It opens in new window">CrossRef
12. Kim, JW, Kim, JY, Kim, JE, Kim, SK, Chung, HT, Park, CK (2014) HOXA10 is associated with temozolomide resistance through regulation of the homologous recombinant DNA repair pathway in glioblastoma cell lines. Genes Cancer 5: pp. 165-74
13. Krivtsov, AV, Twomey, D, Feng, Z, Stubbs, MC, Wang, Y, Faber, J (2006) Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 442: pp. 818-22 ternal" href="http://dx.doi.org/10.1038/nature04980" target="_blank" title="It opens in new window">CrossRef
14. Montavon, T, Duboule, D (2013) Chromatin organization and global regulation of Hox gene clusters. Philos Trans R Soc Lond B Biol Sci 368: pp. 20120367 ternal" href="http://dx.doi.org/10.1098/rstb.2012.0367" target="_blank" title="It opens in new window">CrossRef
15. Wigle, JT, Eisenstat, DD (2008) Homeobox genes in vertebrate forebrain development and disease. Clin Genet 73: pp. 212-26 ternal" href="http://dx.doi.org/10.1111/j.1399-0004.2008.00967.x" target="_blank" title="It opens in new window">CrossRef
16. Alcantara Llaguno, S, Chen, J, Kwon, CH, Jackson, EL, Li, Y, Burns, DK (2009) Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 15: pp. 45-56 ternal" href="http://dx.doi.org/10.1016/j.ccr.2008.12.006" target="_blank" title="It opens in new window">CrossRef
17. Tsafrir, D, Bacolod, M, Selvanayagam, Z, Tsafrir, I, Shia, J, Zeng, Z (2006) Relationship of gene expression and chromosomal abnormalities in colorectal cancer. Cancer Res 66: pp. 2129-37 ternal" href="http://dx.doi.org/10.1158/0008-5472.CAN-05-2569" target="_blank" title="It opens in new window">CrossRef
18. Nigro, JM, Misra, A, Zhang, L, Smirnov, I, Colman, H, Griffin, C (2005) Integrated array-comparative genomic hybridization and expression array profiles identify clinically relevant molecular subtypes of glioblastoma. Cancer Res 65: pp. 1678-86 ternal" href="http://dx.doi.org/10.1158/0008-5472.CAN-04-2921" target="_blank" title="It opens in new window">CrossRef
19. Ozawa, T, Riester, M, Cheng, Y-K, Huse, JT, Squatrito, M, Helmy, K (2014) Most humannon-GCIMP glioblastoma subtypes evolve from a common proneural-like precursor glioma. Cancer Cell 26: pp. 288-300 ternal" href="http://dx.doi.org/10.1016/j.ccr.2014.06.005" target="_blank" title="It opens in new window">CrossRef
20. Yekta, S, Tabin, CJ, Bartel, DP (2008) MicroRNAs in the Hox network: an apparent link to posterior prevalence. Nat Rev Genet 9: pp. 789-96 ternal" href="http://dx.doi.org/10.1038/nrg2400" target="_blank" title="It opens in new window">CrossRef
21. Verhaak, RG, Hoadley, KA, Purdom, E, Wang, V, Qi, Y, Wilkerson, MD (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17: pp. 98-110 ternal" href="http://dx.doi.org/10.1016/j.ccr.2009.12.020" target="_blank" title="It opens in new window">CrossRef
22. Noushmehr, H, Weisenberger, DJ, Diefes, K, Phillips, HS, Pujara, K, Berman, BP (2010) Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17: pp. 419-20 ternal" href="http://dx.doi.org/10.1016/j.ccr.2010.03.017" target="_blank" title="It opens in new window">CrossRef
23. Hegi, ME, Diserens, AC, Gorlia, T, Hamou, MF, Tribolet, N, Weller, M (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352: pp. 997-1003 ternal" href="http://dx.doi.org/10.1056/NEJMoa043331" target="_blank" title="It opens in new window">CrossRef
24. Bady, P, Sciuscio, D, Diserens, AC, Bloch, J, Bent, MJ, Marosi, C (2012) MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status. Acta Neuropathol 124: pp. 547-60 ternal" href="http://dx.doi.org/10.1007/s00401-012-1016-2" target="_blank" title="It opens in new window">CrossRef
25. Bird, A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16: pp. 6-21 ternal" href="http://dx.doi.org/10.1101/gad.947102" target="_blank" title="It opens in new window">CrossRef
26. Deaton, AM, Bird, A (2011) CpG islands and the regulation of transcription. Genes Dev 25: pp. 1010-22 ternal" href="http://dx.doi.org/10.1101/gad.2037511" target="_blank" title="It opens in new window">CrossRef
27. Li, E, Beard, C, Jaenisch, R (1993) Role for DNA methylation in genomic imprinting. Nature 366: pp. 362-5 ternal" href="http://dx.doi.org/10.1038/366362a0" target="_blank" title="It opens in new window">CrossRef
28. Suzuki, MM, Bird, A (2008) DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9: pp. 465-76 ternal" href="http://dx.doi.org/10.1038/nrg2341" target="_blank" title="It opens in new window">CrossRef
29. Noordermeer, D, Leleu, M, Splinter, E, Rougemont, J, Laat, W, Duboule, D (2011) The dynamic architecture of Hox gene clusters. Science 334: pp. 222-5 ternal" href="http://dx.doi.org/10.1126/science.1207194" target="_blank" title="It opens in new window">CrossRef
30. Margueron, R, Reinberg, D (2011) The Polycomb complex PRC2 and its mark in life. Nature 469: pp. 343-9 ternal" href="http://dx.doi.org/10.1038/nature09784" target="_blank" title="It opens in new window">CrossRef
31. Akiva, P, Toporik, A, Edelheit, S, Peretz, Y, Diber, A, Shemesh, R (2006) Transcription-mediated gene fusion in the human genome. Genome Res 16: pp. 30-6 ternal" href="http://dx.doi.org/10.1101/gr.4137606" target="_blank" title="It opens in new window">CrossRef
32. Mainguy, G, Koster, J, Woltering, J, Jansen, H, Durston, A (2007) Extensive polycistronism and antisense transcription in the mammalian Hox clusters. PLoS One 2: pp. e356 ternal" href="http://dx.doi.org/10.1371/journal.pone.0000356" target="_blank" title="It opens in new window">CrossRef
33. Prakash, T, Sharma, VK, Adati, N, Ozawa, R, Kumar, N, Nishida, Y (2010) Expression of conjoined genes: another mechanism for gene regulation in eukaryotes. PLoS One 5: pp. e13284 ternal" href="http://dx.doi.org/10.1371/journal.pone.0013284" target="_blank" title="It opens in new window">CrossRef
34. Calin, GA, Sevignani, C, Dumitru, CD, Hyslop, T, Noch, E, Yendamuri, S (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 101: pp. 2999-3004 ternal" href="http://dx.doi.org/10.1073/pnas.0307323101" target="_blank" title="It opens in new window">CrossRef
35. Rinn, JL, Kertesz, M, Wang, JK, Squazzo, SL, Xu, X, Brugmann, SA (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129: pp. 1311-23 ternal" href="http://dx.doi.org/10.1016/j.cell.2007.05.022" target="_blank" title="It opens in new window">CrossRef
36. Wang, KC, Yang, YW, Liu, B, Sanyal, A, Corces-Zimmerman, R, Chen, Y (2011) A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472: pp. 120-4 ternal" href="http://dx.doi.org/10.1038/nature09819" target="_blank" title="It opens in new window">CrossRef
37. Sessa, L, Breiling, A, Lavorgna, G, Silvestri, L, Casari, G, Orlando, V (2007) Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster. RNA 13: pp. 223-39 ternal" href="http://dx.doi.org/10.1261/rna.266707" target="_blank" title="It opens in new window">CrossRef
38. Zhang, X, Lian, Z, Padden, C, Gerstein, MB, Rozowsky, J, Snyder, M (2009) A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster. Blood 113: pp. 2526-34 ternal" href="http://dx.doi.org/10.1182/blood-2008-06-162164" target="_blank" title="It opens in new window">CrossRef
39. Stupp, R, Dietrich, P, Ostermann Kraljevic, S, Pica, A, Maillard, I, Maeder, P (2002) Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 20: pp. 1375-82 ternal" href="http://dx.doi.org/10.1200/JCO.20.5.1375" target="_blank" title="It opens in new window">CrossRef
40. Stupp, R, Mason, WP, Bent, MJ, Weller, M, Fisher, B, Taphoorn, MJB (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352: pp. 987-96 ternal" href="http://dx.doi.org/10.1056/NEJMoa043330" target="_blank" title="It opens in new window">CrossRef
World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 310: pp. 2191-4 ternal" href="http://dx.doi.org/10.1001/jama.2013.281053" target="_blank" title="It opens in new window">CrossRef
41. Sciuscio, D, Diserens, AC, Dommelen, K, Martinet, D, Jones, G, Janzer, RC (2011) Extent and patterns of MGMT promoter methylation in glioblastoma- and respective glioblastoma-derived spheres. Clin Cancer Res 17: pp. 255-66 ternal" href="http://dx.doi.org/10.1158/1078-0432.CCR-10-1931" target="_blank" title="It opens in new window">CrossRef
42. Bady, P, Diserens, AC, Castella, V, Kalt, S, Heinimann, K, Hamou, MF (2012) DNA fingerprinting of glioma cell lines and considerations on similarity measurements. Neuro Oncol 14: pp. 701-11 ternal" href="http://dx.doi.org/10.1093/neuonc/nos072" target="_blank" title="It opens in new window">CrossRef
43. UCSF - array core service - human BAC arrays. [ttp://cancer.ucsf.edu/research/cores/array/array-services#humanBAC" class="a-plus-plus">http://cancer.ucsf.edu/research/cores/array/array-services#humanBAC]
44. A language and environment for statistical computing. [ttp://www.R-project.org/" class="a-plus-plus">http://www.R-project.org/]
45. Du, P, Zhang, X, Huang, CC, Jafari, N, Kibbe, WA, Hou, L (2010) Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis. BMC Bioinformatics 11: pp. 587 ternal" href="http://dx.doi.org/10.1186/1471-2105-11-587" target="_blank" title="It opens in new window">CrossRef
46. Bioconductor - open source software for bioinformatics. [ttp://www.bioconductor.org/" class="a-plus-plus">http://www.bioconductor.org/]
47. Cali艅ski, T, Harabasz, J (1974) A dendrite method for cluster analysis. Commun Stat 3: pp. 1-27 ternal" href="http://dx.doi.org/10.1080/03610928308827180" target="_blank" title="It opens in new window">CrossRef
48. Lambiv, WL, Vassallo, I, Delorenzi, M, Shay, T, Diserens, AC, Misra, A (2011) The Wnt inhibitory factor 1 (WIF1) is targeted in glioblastoma and has a tumor suppressing function potentially by induction of senescence. Neuro Oncol 13: pp. 736-47 ternal" href="http://dx.doi.org/10.1093/neuonc/nor036" target="_blank" title="It opens in new window">CrossRef
49. Gene Expression Omnibus. [ttp://www.ncbi.nlm.nih.gov/geo/" class="a-plus-plus">http://www.ncbi.nlm.nih.gov/geo/]
Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455: pp. 1061-8 ternal" href="http://dx.doi.org/10.1038/nature07385" target="_blank" title="It opens in new window">CrossRef
50. The cancer genome atlas. [ttp://tcga-data.nci.nih.gov/tcga/tcgaHome2.jsp" class="a-plus-plus">http://tcga-data.nci.nih.gov/tcga/tcgaHome2.jsp] - 刊物主题：Animal Genetics and Genomics; Human Genetics; Plant Genetics & Genomics; Microbial Genetics and Genomics; Fungus Genetics; Bioinformatics;
- 出版者：BioMed Central
- ISSN：1465-6906
文摘
Background HOX genes are a family of developmental genes that are expressed neither in the developing forebrain nor in the normal brain. Aberrant expression of a HOX-gene dominated stem-cell signature in glioblastoma has been linked with increased resistance to chemo-radiotherapy and sustained proliferation of glioma initiating cells. Here we describe the epigenetic and genetic alterations and their interactions associated with the expression of this signature in glioblastoma. Results We observe prominent hypermethylation of the HOXA locus 7p15.2 in glioblastoma in contrast to non-tumoral brain. Hypermethylation is associated with a gain of chromosome 7, a hallmark of glioblastoma, and may compensate for tumor-driven enhanced gene dosage as a rescue mechanism by preventing undue gene expression. We identify the CpG island of the HOXA10 alternative promoter that appears to escape hypermethylation in the HOX-high glioblastoma. An additive effect of gene copy gain at 7p15.2 and DNA methylation at key regulatory CpGs in HOXA10 is significantly associated with HOX-signature expression. Additionally, we show concordance between methylation status and presence of active or inactive chromatin marks in glioblastoma-derived spheres that are HOX-high or HOX-low, respectively. Conclusions Based on these findings, we propose co-evolution and interaction between gene copy gain, associated with a gain of chromosome 7, and additional epigenetic alterations as key mechanisms triggering a coordinated, but inappropriate, HOX transcriptional program in glioblastoma.