| BMC Cancer | |
| Chromosomal imbalances in human bladder urothelial carcinoma: similarities and differences between biopsy samples and cancer stem-like cells | |
| Donatella Conconi3  Elena Panzeri3  Serena Redaelli3  Giorgio Bovo2  Paolo Viganò1  Guido Strada1  Leda Dalprà3  Angela Bentivegna3  | |
| [1] Urology Division, Bassini Icp Hospital, Milano, Italy | |
| [2] Depatment of Pathology, S. Gerardo Hospital, Monza, Italy | |
| [3] Department of Surgery and Translational Medicine, University of Milan-Bicocca, via Cadore 48, 20052 Monza, Italy | |
| 关键词: cancer stem like-cells; DNA copy number alterations; Array Comparative Genomic Hybridization; Transitional Cell Carcinoma; | |
| Others : 1121135 DOI : 10.1186/1471-2407-14-646 |
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| received in 2014-04-24, accepted in 2014-08-20, 发布年份 2014 | |
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【 摘 要 】
Background
The existence of two distinct groups of tumors with different clinical characteristic is a remarkable feature of transitional cell carcinomas (TCCs) of the bladder. More than 70% are low-grade (LG) non-infiltrating (NI) cancers at diagnosis, but 60-80% of them recur at least one time and 10-20% progress in stage and grade. On the other hand, about 20% of tumors show muscle invasion (IN) and have a poor prognosis with <50% survival after 5 years. This study focuses on the complexity of the bladder cancer genome, and for the first time to our knowledge, on the possibility to compare genomic alterations of in vitro selected cancer stem-like cells (CSCs), and their original biopsy in order to identify different genomic signature already present in the early stages of tumorigenesis of LG and HG tumors.
Methods
We initially used conventional chromosome analysis on TCC biopsies with different histotypes (LG vs HG) in order to detect rough differences between them. Then, we performed array comparative genomic hybridization (aCGH) on 10 HG and 10 LG tumors providing an overview of copy number alterations (CNAs). Finally, we made a comparison of the overall CNAs in 16 biopsies and their respective CSCs isolated from them.
Results
Our findings indicate that LG and HG bladder cancer differ with regard to their genomic profile even in the early stage of tumorigenesis; moreover, we identified a subgroup of LG samples with a higher tendency to lose genomic regions which could represent a more aggressive phenotype.
Conclusions
The outcomes not only provide valuable information to deeper studying TCC carcinogenesis, but also could help in the clinic for diagnosis and prognosis of patients who will benefit from a more aggressive therapy.
【 授权许可】
2014 Conconi et al.; licensee BioMed Central Ltd.
【 预 览 】
| Files | Size | Format | View |
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| 20150211021642172.pdf | 1442KB | ||
| Figure 4. | 89KB | Image | |
| Figure 3. | 80KB | Image | |
| Figure 2. | 84KB | Image | |
| Figure 1. | 117KB | Image |
【 图 表 】
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【 参考文献 】
- [1]Kawanishi H, Takahashi T, Ito M, Matsui Y, Watanabe J, Ito N, Kamoto T, Kadowaki T, Tsujimoto G, Imoto I, Inazawa J, Nishiyama H, Ogawa O: Genetic analysis of multifocal superficial urothelial cancers by array-based comparative genomic hybridisation. Br J Cancer 2007, 97(2):260-266.
- [2]Wu XR: Urothelial tumorigenesis: a tale of divergent pathways. Nat Rev Cancer 2005, 5(9):713-725.
- [3]Goebell PJ, Knowles MA: Bladder cancer or bladder cancers? Genetically distinct malignant conditions of the urothelium. Urol Oncol 2010, 28(4):409-428.
- [4]Billerey C, Chopin D, Aubriot-Lorton MH, Ricol D, de Gil Diez Medina S, Van Rhijn B, Bralet MP, Lefrere-Belda MA, Lahaye JB, Abbou CC, Bonaventure J, Zafrani ES, van der Kwast T, Thiery JP, Radvanyi F: Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. Am J Pathol 2001, 158(6):1955-1959.
- [5]Bakkar AA, Wallerand H, Radvanyi F, Lahaye JB, Pissard S, Lecerf L, Kouyoumdjian JC, Abbou CC, Pairon JC, Jaurand MC, Thiery JP, Chopin DK, de Medina SG: FGFR3 and TP53 gene mutations define two distinct pathways in urothelial cell carcinoma of the bladder. Cancer Res 2003, 63(23):8108-8112.
- [6]Cordon-Cardo C, Wartinger D, Petrylak D, Dalbagni G, Fair WR, Fuks Z, Reuter VE: Altered expression of the retinoblastoma gene product: prognostic indicator in bladder cancer. J Natl Cancer Inst 1992, 84(16):1251-1256.
- [7]Proctor AJ, Coombs LM, Cairns JP, Knowles MA: Amplification at chromosome 11q13 in transitional cell tumours of the bladder. Oncogene 1991, 6(5):789-795.
- [8]Bringuier PP, Tamimi Y, Schuuring E, Schalken J: Expression of cyclin D1 and EMS1 in bladder tumours; relationship with chromosome 11q13 amplification. Oncogene 1996, 12(8):1747-1753.
- [9]Coombs LM, Pigott DA, Sweeney E, Proctor AJ, Eydmann ME, Parkinson C, Knowles MA: Amplification and over-expression of c-erbB-2 in transitional cell carcinoma of the urinary bladder. Br J Cancer 1991, 63(4):601-608.
- [10]Simon R, Struckmann K, Schraml P, Wagner U, Forster T, Moch H, Fijan A, Bruderer J, Wilber K, Mihatsch MJ, Gasser T, Sauter G: Amplification pattern of 12q13-q15 genes (MDM2, CDK4, GLI) in urinary bladder cancer. Oncogene 2002, 21(16):2476-2483.
- [11]Bruch J, Schulz WA, Häussler J, Melzner I, Brüderlein S, Möller P, Kemmerling R, Vogel W, Hameister H: Delineation of the 6p22 amplification unit in urinary bladder carcinoma cell lines. Cancer Res 2000, 60(16):4526-4530.
- [12]Knowles MA: The genetics of transitional cell carcinoma: progress and potential clinical application. BJU Int 1999, 84(4):412-427.
- [13]Nascimento e Pontes MG, da Silveira SM, Trindade Filho JC, Rogatto SR, de Viana Camargo JL: Chromosomal imbalances in successive moments of human bladder urothelial carcinoma. Urol Oncol 2013, 31(6):827-835.
- [14]Chekaluk Y, Wu CL, Rosenberg J, Riester M, Dai Q, Lin S, Guo Y, McDougal WS, Kwiatkowski DJ: Identification of nine genomic regions of amplification in urothelial carcinoma, correlation with stage, and potential prognostic and therapeutic value. PLoS One 2013, 8(4):e60927.
- [15]Blaveri E, Brewer JL, Roydasgupta R, Fridlyand J, DeVries S, Koppie T, Pejavar S, Mehta K, Carroll P, Simko JP, Waldman FM: Bladder cancer stage and outcome by array-based comparative genomic hybridization. Clin Cancer Res 2005, 11(19 Pt 1):7012-7022.
- [16]Shen H, Morrison CD, Zhang J, Underwood W, Yang N, Frangou C, Eng K, Head K, Bollag RJ, Kavuri SK, Rojiani AM, Li Y, Yan L, Hill A, Woloszynska-Read A, Wang J, Liu S, Trump DL, Candace JS: 6p22.3 amplification as a biomarker and potential therapeutic target of advanced stage bladder cancer. Oncotarget 2013, 4(11):2124-2134.
- [17]Nord H, Segersten U, Sandgren J, Wester K, Busch C, Menzel U, Komorowski J, Dumanski JP, Malmström PU, de Díaz Ståhl T: Focal amplifications are associated with high grade and recurrences in stage Ta bladder carcinoma. Int J Cancer 2010, 126(6):1390-1402.
- [18]Chan KS, Espinosa I, Chao M, Wong D, Ailles L, Diehn M, Gill H, Presti J, Chang HY, van de Rijn M, Shortliffe L, Weissman IL: Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc Natl Acad Sci U S A 2009, 106(33):14016-14021.
- [19]Ning ZF, Huang YJ, Lin TX, Zhou YX, Jiang C, Xu KW, Huang H, Yin XB, Huang J: Subpopulations of stem-like cells in side population cells from the human bladder transitional cell cancer cell line T24. J Int Med Res 2009, 37(3):621-630.
- [20]She JJ, Zhang PG, Wang ZM, Gan WM, Che XM: Identification of side population cells from bladder cancer cells by DyeCycle Violet staining. Cancer Biol Ther 2008, 7(10):1663-1668.
- [21]Yang YM, Chang JW: Bladder cancer initiating cells (BCICs) are among EMA-CD44v6+ subset: novel methods for isolating undetermined cancer stem (initiating) cells. Cancer Invest 2008, 26(7):725-733.
- [22]Dancik GM, Owens CR, Iczkowski KA, Theodorescu D: A cell of origin gene signature indicates human bladder cancer has distinct cellular progenitors. Stem Cells 2014, 32(4):974-982.
- [23]Li Y, Laterra J: Cancer stem cells: distinct entities or dynamically regulated phenotypes? Cancer Res 2012, 72(3):576-580.
- [24]Epstein JI, Amin MB, Reuter VR, Mostofi FK: The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol 1998, 22(12):1435-1448.
- [25]Bentivegna A, Conconi D, Panzeri E, Sala E, Bovo G, Viganò P, Brunelli S, Bossi M, Tredici G, Strada G, Dalprà L: Biological heterogeneity of putative bladder cancer stem-like cell populations from human bladder transitional cell carcinoma samples. Cancer Sci 2010, 101(2):416-424.
- [26]Cheung SW, Shaw CA, Scott DA, Patel A, Sahoo T, Bacino CA, Pursley A, Li J, Erickson R, Gropman AL, Miller DT, Seashore MR, Summers AM, Stankiewicz P, Chinault AC, Lupski JR, Beaudet AL, Sutton VR: Microarray-based CGH detects chromosomal mosaicism not revealed by conventional cytogenetics. Am J Med Genet A 2007, 143A(15):1679-1686.
- [27]Beissbarth T, Speed TP: GOstat: find statistically overrepresented Gene Ontologies within a group of genes. Bioinformatics 2004, 20(9):1464-1465.
- [28]Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, Morsberger LA, Iacobuzio-Donahue C, Follows GA, Green AR, Flanagan AM, Stratton MR, et al.: Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 2011, 144(1):27-40.
- [29]Minner S, Kilgué A, Stahl P, Weikert S, Rink M, Dahlem R, Fisch M, Höppner W, Wagner W, Bokemeyer C, Terracciano L, Simon R, Sauter G, Wilczak W: Y chromosome loss is a frequent early event in urothelial bladder cancer. Pathology 2010, 42(4):356-359.
- [30]Panani AD, Roussos C: Sex chromosome abnormalities in bladder cancer: Y polysomies are linked to PT1-grade III transitional cell carcinoma. Anticancer Res 2006, 26(1A):319-323.
- [31]Parkin DM: Global cancer statistics in the year 2000. Lancet Oncol 2001, 2(9):533-543.
- [32]Morrison CD, Liu P, Woloszynska-Read A, Zhang J, Luo W, Qin M, Bshara W, Conroy JM, Sabatini L, Vedell P, Xiong D, Liu S, Wang J, Shen H, Li Y, Omilian AR, Hill A, Head K, Guru K, Kunnev D, Leach R, Eng KH, Darlak C, Hoeflich C, Veeranki S, Glenn S, You M, Pruitt SC, Johnson CS, Trump DL: Whole-genome sequencing identifies genomic heterogeneity at a nucleotide and chromosomal level in bladder cancer. Proc Natl Acad Sci U S A 2014, 111(6):E672-81.
- [33]Kinsella M, Patel A, Bafna V: The elusive evidence for chromothripsis. Nucleic Acids Res 2014.
- [34]Panzeri E, Conconi D, Antolini L, Redaelli S, Valsecchi MG, Bovo G, Pallotti F, Viganò P, Strada G, Dalprà L, Bentivegna A: Chromosomal aberrations in bladder cancer: Fresh versus formalin fixed paraffin embedded tissue and targeted FISH versus wide microarray-based CGH analysis. PLoS One 2011, 6(9):e24237.
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