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Cellular Oncology
Published in: Cellular Oncology 3/2011

Open Access 01-06-2011 | Original Paper

Deletion of chromosome 4q predicts outcome in Stage II colon cancer patients

Authors: R. P. M. Brosens, E. J. T. H. Belt, J. C. Haan, T. E. Buffart, B. Carvalho, H. Grabsch, P. Quirke, M. A. Cuesta, A. F. Engel, B. Ylstra, G. A. Meijer

Published in: Cellular Oncology | Issue 3/2011

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Abstract

Background

Around 30% of all stage II colon cancer patients will relapse and die of their disease. At present no objective parameters to identify high-risk stage II colon cancer patients, who will benefit from adjuvant chemotherapy, have been established. With traditional histopathological features definition of high-risk stage II colon cancer patients is inaccurate. Therefore more objective and robust markers for prediction of relapse are needed. DNA copy number aberrations have proven to be robust prognostic markers, but have not yet been investigated for this specific group of patients. The aim of the present study was to identify chromosomal aberrations that can predict relapse of tumor in patients with stage II colon cancer.

Materials and methods

DNA was isolated from 40 formaldehyde fixed paraffin embedded stage II colon cancer samples with extensive clinicopathological data. Samples were hybridized using Comparative Genomic Hybridization (CGH) arrays to determine DNA copy number changes and microsatellite stability was determined by PCR. To analyze differences between stage II colon cancer patients with and without relapse of tumor a Wilcoxon rank-sum test was implemented with multiple testing correction.

Results

Stage II colon cancers of patients who had relapse of disease showed significantly more losses on chromosomes 4, 5, 15q, 17q and 18q. In the microsatellite stable (MSS) subgroup (n = 28), only loss of chromosome 4q22.1-4q35.2 was significantly associated with disease relapse (P < 0.05, FDR < 0.15). No differences in clinicopathological characteristics between patients with and without relapse were observed.

Conclusion

In the present series of MSS stage II colon cancer patients losses on 4q22.1-4q35.2 were associated with worse outcome and these genomic alterations may aid in selecting patients for adjuvant therapy.
Literature
1.
F. Al-Mulla, S. AlFadhli, A.H. Al-Hakim, J.J. Going, M.S. Bitar, Metastatic recurrence of early-stage colorectal cancer is linked to loss of heterozygosity on chromosomes 4 and 14q. J. Clin. Pathol. 59, 624–630 (2006)PubMedCrossRef
2.
F. Al-Mulla, A.I. Behbehani, M.S. Bitar, G. Varadharaj, J.J. Going, Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse. Mod. Pathol. 19, 648–658 (2006)PubMedCrossRef
3.
H.E. Alcock, T.J. Stephenson, J.A. Royds, D.W. Hammond, Analysis of colorectal tumor progression by microdissection and comparative genomic hybridization. Genes Chromosom. Cancer 37, 369–380 (2003)PubMedCrossRef
4.
A. Barrier, F. Roser, P.Y. Boelle, B. Franc, C. Tse, D. Brault, F. Lacaine, S. Houry, P. Callard, C. Penna, B. Debuire, A. Flahault, S. Dudoit, A. Lemoine, Prognosis of stage II colon cancer by non-neoplastic mucosa gene expression profiling. Oncogene 26, 2642–2648 (2007)PubMedCrossRef
5.
A.B. Benson III, D. Schrag, M.R. Somerfield, A.M. Cohen, A.T. Figueredo, P.J. Flynn, M.K. Krzyzanowska, J. Maroun, P. McAllister, C.E. Van, M. Brouwers, M. Charette, D.G. Haller, American society of clinical oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J. Clin. Oncol. 22, 3408–3419 (2004)PubMedCrossRef
6.
T.E. Buffart, D. Israeli, M. Tijssen, S.J. Vosse, A. Mrsic, G.A. Meijer, B. Ylstra, Across array comparative genomic hybridization: a strategy to reduce reference channel hybridizations. Genes Chromosom. Cancer 47, 994–1004 (2008)PubMedCrossRef
7.
J. Camps, M. Grade, Q.T. Nguyen, P. Hormann, S. Becker, A.B. Hummon, V. Rodriguez, S. Chandrasekharappa, Y. Chen, M.J. Difilippantonio, H. Becker, B.M. Ghadimi, T. Ried, Chromosomal breakpoints in primary colon cancer cluster at sites of structural variants in the genome. Cancer Res. 68, 1284–1295 (2008)PubMedCrossRef
8.
B. Carvalho, C. Postma, S. Mongera, E. Hopmans, S. Diskin, M.A. van de Wiel, C.W. van, O. Thas, A. Matthai, M.A. Cuesta, J.S. Terhaar Sive Droste, M. Craanen, E. Schrock, B. Ylstra and G.A. Meijer, Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression, Gut 58 (2009), 79–89
9.
E. Cetin, B. Cengiz, E. Gunduz, M. Gunduz, H. Nagatsuka, L. Bekir-Beder, K. Fukushima, D. Pehlivan, N. MO, K. Nishizaki, K. Shimizu, N. Nagai, Deletion mapping of chromosome 4q22-35 and identification of four frequently deleted regions in head and neck cancers. Neoplasma 55, 299–304 (2008)PubMed
10.
C. Compton, C.M. Fenoglio-Preiser, N. Pettigrew, L.P. Fielding, American joint committee on cancer prognostic factors consensus conference: colorectal working group. Cancer 88, 1739–1757 (2000)PubMedCrossRef
11.
P.M. De Angelis, T. Stokke, M. Beigi, O. Mjaland, O.P. Clausen, Prognostic significance of recurrent chromosomal aberrations detected by comparative genomic hybridization in sporadic colorectal cancer. Int. J. Colorectal Dis. 16, 38–45 (2001)PubMedCrossRef
12.
C.B. Diep, K. Kleivi, F.R. Ribeiro, M.R. Teixeira, O.C. Lindgjaerde, R.A. Lothe, The order of genetic events associated with colorectal cancer progression inferred from meta-analysis of copy number changes. Genes Chromosom. Cancer 45, 31–41 (2006)PubMedCrossRef
13.
A. Dupuy, R.M. Simon, Critical review of published microarray studies for cancer outcome and guidelines on statistical analysis and reporting. J. Natl Cancer Inst. 99, 147–157 (2007)PubMedCrossRef
14.
A. Figueredo, M.L. Charette, J. Maroun, M.C. Brouwers, L. Zuraw, Adjuvant therapy for stage II colon cancer: a systematic review from the cancer care Ontario program in evidence-based care’s gastrointestinal cancer disease site group. J. Clin. Oncol. 22, 3395–3407 (2004)PubMedCrossRef
15.
K.S. Garman, C.R. Acharya, E. Edelman, M. Grade, J. Gaedcke, S. Sud, W. Barry, A.M. Diehl, D. Provenzale, G.S. Ginsburg, B.M. Ghadimi, T. Ried, J.R. Nevins, S. Mukherjee, D. Hsu, A. Potti, A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities. Proc. Natl. Acad. Sci. U.S.A. 105, 19432–19437 (2008)PubMedCrossRef
16.
S. George, J. Primrose, R. Talbot, J. Smith, M. Mullee, D. Bailey, B.C. Du, H. Jordan, Will Rogers revisited: prospective observational study of survival of 3592 patients with colorectal cancer according to number of nodes examined by pathologists. Br. J. Cancer 95, 841–847 (2006)PubMedCrossRef
17.
S. Gill, C.L. Loprinzi, D.J. Sargent, S.D. Thome, S.R. Alberts, D.G. Haller, J. Benedetti, G. Francini, L.E. Shepherd, S.J. Francois, R. Labianca, W. Chen, S.S. Cha, M.P. Heldebrant, R.M. Goldberg, Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J. Clin. Oncol. 22, 1797–1806 (2004)PubMedCrossRef
18.
M.Y. Kim, S.H. Yim, M.S. Kwon, T.M. Kim, S.H. Shin, H.M. Kang, C. Lee, Y.J. Chung, Recurrent genomic alterations with impact on survival in colorectal cancer identified by genome-wide array comparative genomic hybridization. Gastroenterology 131, 1913–1924 (2006)PubMedCrossRef
19.
T. Knosel, K. Schluns, U. Stein, H. Schwabe, P.M. Schlag, M. Dietel, I. Petersen, Genetic imbalances with impact on survival in colorectal cancer patients. Histopathology 43, 323–331 (2003)PubMedCrossRef
20.
K. Kurashina, Y. Yamashita, T. Ueno, K. Koinuma, J. Ohashi, H. Horie, Y. Miyakura, T. Hamada, H. Haruta, H. Hatanaka, M. Soda, Y.L. Choi, S. Takada, Y. Yasuda, H. Nagai, H. Mano, Chromosome copy number analysis in screening for prognosis-related genomic regions in colorectal carcinoma. Cancer Sci. 99, 1835–1840 (2008)PubMedCrossRef
21.
G. Lanza, M. Matteuzzi, R. Gafa, E. Orvieto, I. Maestri, A. Santini, S.L. Del, Chromosome 18q allelic loss and prognosis in stage II and III colon cancer. Int. J. Cancer 79, 390–395 (1998)PubMedCrossRef
22.
G.J. Liefers, A.M. Cleton-Jansen, d. van, V, J. Hermans, J.H. van Krieken, C.J. Cornelisse and R.A. Tollenaar, Micrometastases and survival in stage II colorectal cancer, N.Engl.J.Med. 339 (1998), 223–228
23.
X.P. Liu, S. Kawauchi, A. Oga, T. Sato, K. Ikemoto, E. Ikeda, K. Sasaki, Chromosomal aberrations detected by comparative genomic hybridization predict outcome in patients with colorectal carcinoma. Oncol. Rep. 17, 261–267 (2007)PubMed
24.
E. Mamounas, S. Wieand, N. Wolmark, H.D. Bear, J.N. Atkins, K. Song, J. Jones, H. Rockette, Comparative efficacy of adjuvant chemotherapy in patients with Dukes’ B versus Dukes’ C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04). J. Clin. Oncol. 17, 1349–1355 (1999)PubMed
25.
E. Martinez-Lopez, A. Abad, A. Font, M. Monzo, I. Ojanguren, A. Pifarre, J.J. Sanchez, C. Martin, R. Rosell, Allelic loss on chromosome 18q as a prognostic marker in stage II colorectal cancer. Gastroenterology 114, 1180–1187 (1998)PubMedCrossRef
26.
S. Matsui, J. Laduca, M.R. Rossi, N.J. Nowak, J.K. Cowell, Molecular characterization of a consistent 4.5-megabase deletion at 4q28 in prostate cancer cells. Cancer Genet. Cytogenet. 159, 18–26 (2005)PubMedCrossRef
27.
G.A. Meijer, M.A. Hermsen, J.P. Baak, P.J. van Diest, S.G. Meuwissen, J.A. Belien, J.M. Hoovers, H. Joenje, P.J. Snijders, J.M. Walboomers, Progression from colorectal adenoma to carcinoma is associated with non-random chromosomal gains as detected by comparative genomic hybridisation. J. Clin. Pathol. 51, 901–909 (1998)PubMedCrossRef
28.
E. Morris, N.J. Maughan, D. Forman, P. Quirke, Who to treat with adjuvant therapy in Dukes B/Stage II colorectal cancer? - The need for high quality pathology. Gut 56, 1419–1425 (2007)PubMedCrossRef
29.
K. Nakao, K.R. Mehta, J. Fridlyand, D.H. Moore, A.N. Jain, A. Lafuente, J.W. Wiencke, J.P. Terdiman, F.M. Waldman, High-resolution analysis of DNA copy number alterations in colorectal cancer by array-based comparative genomic hybridization. Carcinogenesis 25, 1345–1357 (2004)PubMedCrossRef
30.
V.C. Petersen, K.J. Baxter, S.B. Love, N.A. Shepherd, Identification of objective pathological prognostic determinants and models of prognosis in Dukes’ B colon cancer. Gut 51, 65–69 (2002)PubMedCrossRef
31.
T.J. Polascik, P. Cairns, W.Y. Chang, M.P. Schoenberg, D. Sidransky, Distinct regions of allelic loss on chromosome 4 in human primary bladder carcinoma. Cancer Res. 55, 5396–5399 (1995)PubMed
32.
M. Sheffer, M.D. Bacolod, O. Zuk, S.F. Giardina, H. Pincas, F. Barany, P.B. Paty, W.L. Gerald, D.A. Notterman, E. Domany, Association of survival and disease progression with chromosomal instability: a genomic exploration of colorectal cancer. Proc. Natl. Acad. Sci. U.S.A. 106, 7131–7136 (2009)PubMedCrossRef
33.
N. Shivapurkar, S. Sood, I.I. Wistuba, A.K. Virmani, A. Maitra, S. Milchgrub, J.D. Minna, A.F. Gazdar, Multiple regions of chromosome 4 demonstrating allelic losses in breast carcinomas. Cancer Res. 59, 3576–3580 (1999)PubMed
34.
L.H. Sobin, I.D. Fleming, TNM Classification of Malignant Tumors, fifth edition, Union internationale contre le cancer and the American joint committee on cancer. Cancer 80, 1803–1804 (1997)PubMedCrossRef
35.
K. Trautmann, J.P. Terdiman, A.J. French, R. Roydasgupta, N. Sein, S. Kakar, J. Fridlyand, A.M. Snijders, D.G. Albertson, S.N. Thibodeau, F.M. Waldman, Chromosomal instability in microsatellite-unstable and stable colon cancer. Clin. Cancer Res. 12, 6379–6385 (2006)PubMedCrossRef
36.
D. Tsafrir, M. Bacolod, Z. Selvanayagam, I. Tsafrir, J. Shia, Z. Zeng, H. Liu, C. Krier, R.F. Stengel, F. Barany, W.L. Gerald, P.B. Paty, E. Domany, D.A. Notterman, Relationship of gene expression and chromosomal abnormalities in colorectal cancer. Cancer Res. 66, 2129–2137 (2006)PubMedCrossRef
37.
M.A. van de Wiel, K.I. Kim, S.J. Vosse, W.N. van Wieringen, S.M. Wilting, B. Ylstra, CGHcall: calling aberrations for array CGH tumor profiles. Bioinformatics 23, 892–894 (2007)PubMedCrossRef
38.
M.A. van de Wiel, S.J. Smeets, R.H. Brakenhoff, B. Ylstra, CGHMultiArray: exact P-values for multi-array comparative genomic hybridization data. Bioinformatics 21, 3193–3194 (2005)PubMedCrossRef
39.
M.A. van de Wiel, W.N. van Wieringen, CGHregions: dimension reduction for array CGH data with minimal information loss. Cancer Inform. 3, 55–63 (2007)PubMed
40.
L.N. van Steenbergen, V.E. Lemmens, M.J. Louwman, J.W. Straathof, J.W. Coebergh, Increasing incidence and decreasing mortality of colorectal cancer due to marked cohort effects in southern Netherlands. Eur. J. Cancer Prev. 18, 145–152 (2009)PubMedCrossRef
41.
A. Walther, R. Houlston, I. Tomlinson, Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis. Gut 57, 941–950 (2008)PubMedCrossRef
42.
M.M. Weiss, M.A. Hermsen, G.A. Meijer, N.C. van Grieken, J.P. Baak, E.J. Kuipers, P.J. van Diest, Comparative genomic hybridisation. Mol. Pathol. 52, 243–251 (1999)PubMedCrossRef
43.
J. Weitz, M. Koch, J. Debus, T. Hohler, P.R. Galle, M.W. Buchler, Colorectal cancer. Lancet 365, 153–165 (2005)PubMedCrossRef
44.
R. Winn, J. McClure, The NCCN clinical practice guidelines in oncology. J Natl Comprehensive Cancer Network 1, 5–13 (2003)
45.
B.M. Wolpin, J.A. Meyerhardt, H.J. Mamon, R.J. Mayer, Adjuvant treatment of colorectal cancer. CA Cancer J. Clin. 57, 168–185 (2007)PubMedCrossRef
46.
M. Wrage, S. Ruosaari, P.P. Eijk, J.T. Kaifi, J. Hollmen, E.F. Yekebas, J.R. Izbicki, R.H. Brakenhoff, T. Streichert, S. Riethdorf, M. Glatzel, B. Ylstra, K. Pantel, H. Wikman, Genomic profiles associated with early micrometastasis in lung cancer: relevance of 4q deletion. Clin. Cancer Res. 15, 1566–1574 (2009)PubMedCrossRef
Metadata
Title
Deletion of chromosome 4q predicts outcome in Stage II colon cancer patients
Authors
R. P. M. Brosens
E. J. T. H. Belt
J. C. Haan
T. E. Buffart
B. Carvalho
H. Grabsch
P. Quirke
M. A. Cuesta
A. F. Engel
B. Ylstra
G. A. Meijer
Publication date
01-06-2011
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 3/2011
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-011-0042-8

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