期刊论文详细信息
Radiation Oncology
Genomic alterations in rectal tumors and response to neoadjuvant chemoradiotherapy: an exploratory study
Daniele Calistri1  Dino Amadori3  Massimo Guidoboni6  Luca Saragoni7  Paola Rosetti3  Alessandro Passardi3  Enrico Lucci8  Ermanno Emiliani5  Wainer Zoli1  Massimo Giannini4  Nazario Teodorani5  Michela Ballardini2  Chiara Molinari1 
[1] Biosciences Laboratories, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Meldola, Italy;Unit of Biostatistics and Clinical Trials, I.R.S.T., Meldola, Italy;Department of Medical Oncology, I.R.S.T., Meldola, Italy;Radiotherapy Unit, I.R.S.T., Meldola, Italy;Radiotherapy Unit, Santa Maria delle Croci Hospital, Ravenna, Italy;Immunotherapy and Cell Therapy Laboratory, I.R.S.T., Meldola, Italy;Pathology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy;Department of General Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
关键词: ArrayCGH;    neoadjuvant chemoradiotherapy;    rectal cancer;    Genomic alterations;   
Others  :  1160937
DOI  :  10.1186/1748-717X-6-161
 received in 2011-07-28, accepted in 2011-11-18,  发布年份 2011
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【 摘 要 】

Background

Neoadjuvant chemoradiotherapy is the treatment of choice in advanced rectal cancer, even though there are many patients who will not benefit from it. There are still no effective methods for predicting which patients will respond or not. The present study aimed to define the genomic profile of rectal tumors and to identify alterations that are predictive of response in order to optimize therapeutic strategies.

Methods

Forty-eight candidates for neoadjuvant chemoradiotherapy were recruited and their pretherapy biopsies analyzed by array Comparative Genomic Hybridization (aCGH). Pathologic response was evaluated by tumor regression grade.

Results

Both Hidden Markov Model and Smoothing approaches identified similar alterations, with a prevalence of DNA gains. Non responsive patients had a different alteration profile from responsive ones, with a higher number of genome changes mainly located on 2q21, 3q29, 7p22-21, 7q21, 7q36, 8q23-24, 10p14-13, 13q12, 13q31-34, 16p13, 17p13-12 and 18q23 chromosomal regions.

Conclusions

This exploratory study suggests that an in depth characterization of chromosomal alterations by aCGH would provide useful predictive information on response to neoadjuvant chemoradiotherapy and could help to optimize therapy in rectal cancer patients.

The data discussed in this study are available on the NCBI Gene Expression Omnibus [GEO: GSE25885].

【 授权许可】

   
2011 Molinari et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Bosset JF, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Briffaux A, Collette L: Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results--EORTC 22921. J Clin Oncol 2005, 23:5620-5627.
  • [2]Roh MS, Colangelo LH, O'Connell MJ, Yothers G, Deutsch M, Allegra CJ, Kahlenberg MS, Baez-Diaz L, Ursiny CS, Petrelli NJ, Wolmark N: Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 2009, 27:5124-5130.
  • [3]Balch GC, De Meo A, Guillem JG: Modern management of rectal cancer: a 2006 update. World J Gastroenterol 2006, 12:3186-3195.
  • [4]Jakob C, Aust DE, Meyer W, Baretton GB, Schwabe W, Häusler P, Becker H, Liersch T: Thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase expression, and histological tumour regression after 5-FU-based neo-adjuvant chemoradiotherapy in rectal cancer. J Pathol 2004, 204:562-568.
  • [5]Jakob C, Liersch T, Meyer W, Becker H, Baretton GB, Aust DE: Predictive value of Ki67 and p53 in locally advanced rectal cancer: correlation with thymidylate synthase and histopathological tumor regression after neoadjuvant 5-FU-based chemoradiotherapy. World J Gastroenterol 2008, 14:1060-1066.
  • [6]Kuremsky JG, Tepper JE, McLeod HL: Biomarkers for response to neoadjuvant chemoradiation for rectal cancer. Int J Radiat Oncol Biol Phys 2009, 74:673-688.
  • [7]Ghadimi BM, Grade M, Difilippantonio MJ, Varma S, Simon R, Montagna C, Füzesi L, Langer C, Becker H, Liersch T, Ried T: Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. J Clin Oncol 2005, 23:1826-1838.
  • [8]Kim IJ, Lim SB, Kang HC, Chang HJ, Ahn SA, Park HW, Jang SG, Park JH, Kim DY, Jung KH, Choi HS, Jeong SY, Sohn DK, Kim DW, Park JG: Microarray gene expression profiling for predicting complete response to preoperative chemoradiotherapy in patients with advanced rectal cancer. Dis Colon Rectum 2007, 50:1342-1353.
  • [9]Rimkus C, Friederichs J, Boulesteix AL, Theisen J, Mages J, Becker K, Nekarda H, Rosenberg R, Janssen KP, Siewert JR: Microarray-based prediction of tumor response to neoadjuvant radiochemotherapy of patients with locally advanced rectal cancer. Clin Gastroenterol Hepatol 2008, 6:53-61.
  • [10]Albertson DG: Gene amplification in cancer. Trends Genet 2006, 22:447-455.
  • [11]Grade M, Ghadimi BM, Varma S, Simon R, Wangsa D, Barenboim-Stapleton L, Liersch T, Becker H, Ried T, Difilippantonio MJ: Aneuploidy-dependent massive deregulation of the cellular transcriptome and apparent divergence of the Wnt/beta-catenin signaling pathway in human rectal carcinomas. Cancer Res 2006, 66:267-282.
  • [12]Diep CB, Kleivi K, Ribeiro FR, Teixeira MR, Lindgjaerde OC, Lothe RA: The order of genetic events associated with colorectal cancer progression inferred from meta-analysis of copy number changes. Genes Chromosomes Cancer 2006, 45:31-41.
  • [13]Douglas EJ, Fiegler H, Rowan A, Halford S, Bicknell DC, Bodmer W, Tomlinson IP, Carter NP: Array comparative genomic hybridization analysis of colorectal cancer cell lines and primary carcinomas. Cancer Res 2004, 64:4817-4825.
  • [14]Gaasenbeek M, Howarth K, Rowan AJ, Gorman PA, Jones A, Chaplin T, Liu Y, Bicknell D, Davison EJ, Fiegler H, Carter NP, Roylance RR, Tomlinson IP: Combined array-comparative genomic hybridization and single-nucleotide polymorphism-loss of heterozygosity analysis reveals complex changes and multiple forms of chromosomal instability in colorectal cancers. Cancer Res 2006, 66:3471-3479.
  • [15]Sugai T, Takahashi H, Habano W, Nakamura S, Sato K, Orii S, Suzuki K: Analysis of genetic alterations, classified according to their DNA ploidy pattern, in the progression of colorectal adenomas and early colorectal carcinomas. J Pathol 2003, 200:168-176.
  • [16]Grade M, Gaedcke J, Wangsa D, Varma S, Beckmann J, Liersch T, Hess C, Becker H, Difilippantonio MJ, Ried T, Ghadimi BM: Chromosomal copy number changes of locally advanced rectal cancers treated with preoperative chemoradiotherapy. Cancer Genet Cytogenet 2009, 193:19-28.
  • [17]Lockwood WW, Chari R, Chi B, Lam WL: Recent advances in array comparative genomic hybridization technologies and their applications in human genetics. Eur J Hum Genet 2006, 14:139-148.
  • [18]Pinkel D, Albertson DG: Array comparative genomic hybridization and its applications in cancer. Nat Genet 2005, 37(Suppl):S11-17.
  • [19]Dworak O, Keilholz L, Hoffmann A: Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 1997, 12:19-23.
  • [20]Jong K, Marchiori E, Meijer G, Vaart AV, Ylstra B: Breakpoint identification and smoothing of array comparative genomic hybridization data. Bioinformatics 2004, 20:3636-3637.
  • [21]Fridlyand J, Dimitrov P: [http://www.bioconductor.org/packages/2.8/bioc/html/aCGH.html] webcitePackage: aCGH. Accessed 11.05.11
  • [22]Fridlyand J, Snijders A, Pinkel D, Albertson DG, Jain AN: Hidden Markov Model approach to the analysis of array CGH data. J Multivariate Anal 2004, 90:132-153.
  • [23]R Development Core Team (2008): A language and environment for statistical computing [http://www.R-project.org] webciteR Foundation for Statistical Computing, Vienna, Austria; 2008. ISBN 3-900051-07-0
  • [24]Weiss J, Moghanaki D, Plastaras JP, Haller DG: Improved patient and regimen selection in locally advanced rectal cancer: who, how, and what next? Clin Colorectal Cancer 2009, 8:194-199.
  • [25]Losi L, Luppi G, Gavioli M, Iachetta F, Bertolini F, D'Amico R, Jovic G, Bertoni F, Falchi AM, Conte PF: Prognostic value of Dworak grade of regression (GR) in patients with rectal carcinoma treated with preoperative radiochemotherapy. Int J Colorectal Dis 2006, 21:645-651.
  • [26]Vironen J, Juhola M, Kairaluoma M, Jantunen I, Kellokumpu I: Tumour regression grading in the evaluation of tumour response after different preoperative radiotherapy treatments for rectal carcinoma. Int J Colorectal Dis 2005, 20:440-445.
  • [27]Quah HM, Chou JF, Gonen M, Shia J, Schrag D, Saltz LB, Goodman KA, Minsky BD, Wong WD, Weiser MR: Pathologic stage is most prognostic of disease-free survival in locally advanced rectal cancer patients after preoperative chemoradiation. Cancer 2008, 113:57-64.
  • [28]Bujko K, Kolodziejczyk M, Nasierowska-Guttmejer A, Michalski W, Kepka L, Chmielik E, Wojnar A, Chwalinski M, Polish Colorectal Cancer Group: Tumour regression grading in patients with residual rectal cancer after preoperative chemoradiation. Radiother Oncol 95:298-302.
  • [29]Camps J, Grade M, Nguyen QT, Hörmann P, Becker S, Hummon AB, Rodriguez V, Chandrasekharappa S, Chen Y, Difilippantonio MJ, Becker H, Ghadimi BM, Ried T: Chromosomal breakpoints in primary colon cancer cluster at sites of structural variants in the genome. Cancer Res 2008, 68:1284-1295.
  • [30]Lassmann S, Weis R, Makowiec F, Roth J, Danciu M, Hopt U, Werner M: Array CGH identifies distinct DNA copy number profiles of oncogenes and tumor suppressor genes in chromosomal- and microsatellite-unstable sporadic colorectal carcinomas. J Mol Med 2007, 85:293-304.
  • [31]Nakao K, Mehta KR, Fridlyand J, Moore DH, Jain AN, Lafuente A, Wiencke JW, Terdiman JP, Waldman FM: High-resolution analysis of DNA copy number alterations in colorectal cancer by array-based comparative genomic hybridization. Carcinogenesis 2004, 25:1345-1357.
  • [32]Lips EH, de Graaf EJ, Tollenaar RA, van Eijk R, Oosting J, Szuhai K, Karsten T, Nanya Y, Ogawa S, van de Velde CJ, Eilers PH, van Wezel T, Morreau H: Single nucleotide polymorphism array analysis of chromosomal instability patterns discriminates rectal adenomas from carcinomas. J Pathol 2007, 212:269-277.
  • [33]Korn WM, Yasutake T, Kuo WL, Warren RS, Collins C, Tomita M, Gray J, Waldman FM: Chromosome arm 20q gains and other genomic alterations in colorectal cancer metastatic to liver, as analyzed by comparative genomic hybridization and fluorescence in situ hybridization. Genes Chromosomes Cancer 1999, 25:82-90.
  • [34]Ashktorab H, Schaffer AA, Daremipouran M, Smoot DT, Lee E, Brim H: Distinct genetic alterations in colorectal cancer. PLoS One 2010, 5:e8879.
  • [35]Curtin K, Lin WY, George R, Katory M, Shorto J, Cannon-Albright LA, Smith G, Bishop DT, Cox A, Camp NJ: Genetic variants in XRCC2: new insights into colorectal cancer tumorigenesis. Cancer Epidemiol Biomarkers Prev 2009, 18:2476-2484.
  • [36]Sossey-Alaoui K, Safina A, Li X, Vaughan MM, Hicks DG, Bakin AV, Cowell JK: Down-regulation of WAVE3, a metastasis promoter gene, inhibits invasion and metastasis of breast cancer cells. Am J Pathol 2007, 170:2112-2121.
  • [37]Kurisaki A, Kurisaki K, Kowanetz M, Sugino H, Yoneda Y, Heldin CH, Moustakas A: The mechanism of nuclear export of Smad3 involves exportin 4 and Ran. Mol Cell Biol 2006, 26:1318-1332.
  • [38]Wang Q, Moyret-Lalle C, Couzon F, Surbiguet-Clippe C, Saurin JC, Lorca T, Navarro C, Puisieux A: Alterations of anaphase-promoting complex genes in human colon cancer cells. Oncogene 2003, 22:1486-1490.
  • [39]Habuchi H, Tanaka M, Habuchi O, Yoshida K, Suzuki H, Ban K, Kimata K: The occurrence of three isoforms of heparan sulfate 6-O-sulfotransferase having different specificities for hexuronic acid adjacent to the targeted N-sulfoglucosamine. J Biol Chem 2000, 275:2859-2868.
  • [40]Yu W, Inoue J, Imoto I, Matsuo Y, Karpas A, Inazawa J: GPC5 is a possible target for the 13q31-q32 amplification detected in lymphoma cell lines. J Hum Genet 2003, 48:331-335.
  • [41]Aldred MA, Huang Y, Liyanarachchi S, Pellegata NS, Gimm O, Jhiang S, Davuluri RV, de la Chapelle A, Eng C: Papillary and follicular thyroid carcinomas show distinctly different microarray expression profiles and can be distinguished by a minimum of five genes. J Clin Oncol 2004, 22:3531-3539.
  • [42]Ho LL, Kench JG, Handelsman DJ, Scheffer GL, Stricker PD, Grygiel JG, Sutherland RL, Henshall SM, Allen JD, Horvath LG: Androgen regulation of multidrug resistance-associated protein 4 (MRP4/ABCC4) in prostate cancer. Prostate 2008, 68:1421-1429.
  • [43]Lee K, Klein-Szanto AJ, Kruh GD: Analysis of the MRP4 drug resistance profile in transfected NIH3T3 cells. J Natl Cancer Inst 2000, 92:1934-1940.
  • [44]Schimanski CC, Schmitz G, Kashyap A, Bosserhoff AK, Bataille F, Schäfer SC, Lehr HA, Berger MR, Galle PR, Strand S, Strand D: Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer. Oncogene 2005, 24:3100-3109.
  • [45]Lips EH, van Eijk R, de Graaf EJ, Oosting J, de Miranda NF, Karsten T, van de Velde CJ, Eilers PH, Tollenaar RA, van Wezel T, Morreau H: Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis. BMC Cancer 2008, 8:314. BioMed Central Full Text
  • [46]Watanabe T, Komuro Y, Kiyomatsu T, Kanazawa T, Kazama Y, Tanaka J, Tanaka T, Yamamoto Y, Shirane M, Muto T, Nagawa H: Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles. Cancer Res 2006, 66:3370-3374.
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