Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2010

Open Access 01-12-2010 | Research article

Specific genomic aberrations in primary colorectal cancer are associated with liver metastases

Authors: Sjoerd C Bruin, Christiaan Klijn, Gerrit-Jan Liefers, Linde M Braaf, Simon A Joosse, Eric H van Beers, Victor J Verwaal, Hans Morreau, Lodewyk F Wessels, Marie-Louise F van Velthuysen, Rob AEM Tollenaar, Laura J van't Veer

Published in: BMC Cancer | Issue 1/2010

Login to get access

Abstract

Background

Accurate staging of colorectal cancer (CRC) with clinicopathological parameters is important for predicting prognosis and guiding treatment but provides no information about organ site of metastases. Patterns of genomic aberrations in primary colorectal tumors may reveal a chromosomal signature for organ specific metastases.

Methods

Array Comparative Genomic Hybridization (aCGH) was employed to asses DNA copy number changes in primary colorectal tumors of three distinctive patient groups. This included formalin-fixed, paraffin-embedded tissue of patients who developed liver metastases (LM; n = 36), metastases (PM; n = 37) and a group that remained metastases-free (M0; n = 25).
A novel statistical method for identifying recurrent copy number changes, KC-SMART, was used to find specific locations of genomic aberrations specific for various groups. We created a classifier for organ specific metastases based on the aCGH data using Prediction Analysis for Microarrays (PAM).

Results

Specifically in the tumors of primary CRC patients who subsequently developed liver metastasis, KC-SMART analysis identified genomic aberrations on chromosome 20q. LM-PAM, a shrunken centroids classifier for liver metastases occurrence, was able to distinguish the LM group from the other groups (M0&PM) with 80% accuracy (78% sensitivity and 86% specificity). The classification is predominantly based on chromosome 20q aberrations.

Conclusion

Liver specific CRC metastases may be predicted with a high accuracy based on specific genomic aberrations in the primary CRC tumor. The ability to predict the site of metastases is important for improvement of personalized patient management.
Appendix
Available only for authorised users
Literature
1.
Weitz J, Koch M, Debus J, Hohler T, Galle PR, Buchler MW: Colorectal cancer. Lancet. 2005, 365: 153-165. 10.1016/S0140-6736(05)17706-X.CrossRefPubMed
2.
Abdel-Misih SR, Schmidt CR, Bloomston PM: Update and review of the multidisciplinary management of stage IV colorectal cancer with liver metastases. World J Surg Oncol. 2009, 7: 72-10.1186/1477-7819-7-72.CrossRefPubMedPubMedCentral
3.
Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H: 8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol. 2008, 15: 2426-2432. 10.1245/s10434-008-9966-2.CrossRefPubMed
4.
Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell. 1990, 61: 759-767. 10.1016/0092-8674(90)90186-I.CrossRefPubMed
5.
Lengauer C, Kinzler KW, Vogelstein B: Genetic instability in colorectal cancers. Nature. 1997, 386: 623-627. 10.1038/386623a0.CrossRefPubMed
6.
Jass JR: Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology. 2007, 50: 113-130. 10.1111/j.1365-2559.2006.02549.x.CrossRefPubMed
7.
Jass JR, Whitehall VL, Young J, Leggett BA: Emerging concepts in colorectal neoplasia. Gastroenterology. 2002, 123: 862-876. 10.1053/gast.2002.35392.CrossRefPubMed
8.
Cardoso J, Boer J, Morreau H, Fodde R: Expression and genomic profiling of colorectal cancer. Biochim Biophys Acta. 2007, 1775: 103-137.PubMed
9.
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. 10.1002/gcc.20261.CrossRefPubMed
10.
Hidaka S, Yasutake T, Takeshita H, Kondo M, Tsuji T, Nanashima A, Sawai T, Yamaguchi H, Nakagoe T, Ayabe H, et al: Differences in 20q13.2 copy number between colorectal cancers with and without liver metastasis. Clin Cancer Res. 2000, 6: 2712-2717.PubMed
11.
Aragane H, Sakakura C, Nakanishi M, Yasuoka R, Fujita Y, Taniguchi H, Hagiwara A, Yamaguchi T, Abe T, Inazawa J, et al: Chromosomal aberrations in colorectal cancers and liver metastases analyzed by comparative genomic hybridization. Int J Cancer. 2001, 94: 623-629. 10.1002/ijc.1522.CrossRefPubMed
12.
Aust DE, Muders M, Kohler A, Schmidt M, Diebold J, Muller C, Lohrs U, Waldman FM, Baretton GB: Prognostic relevance of 20q13 gains in sporadic colorectal cancers: a FISH analysis. Scand J Gastroenterol. 2004, 39: 766-772. 10.1080/00365520410003191.CrossRefPubMed
13.
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. 10.1002/(SICI)1098-2264(199906)25:2<82::AID-GCC2>3.0.CO;2-6.CrossRefPubMed
14.
Mehta KR, Nakao K, Zuraek MB, Ruan DT, Bergsland EK, Venook AP, Moore DH, Tokuyasu TA, Jain AN, Warren RS, et al: Fractional genomic alteration detected by array-based comparative genomic hybridization independently predicts survival after hepatic resection for metastatic colorectal cancer. Clin Cancer Res. 2005, 11: 1791-1797. 10.1158/1078-0432.CCR-04-1418.CrossRefPubMed
15.
Arango D, Laiho P, Kokko A, Alhopuro P, Sammalkorpi H, Salovaara R, Nicorici D, Hautaniemi S, Alazzouzi H, Mecklin JP, et al: Gene-expression profiling predicts recurrence in Dukes' C colorectal cancer. Gastroenterology. 2005, 129: 874-884. 10.1053/j.gastro.2005.06.066.CrossRefPubMed
16.
Barrier A, Boelle PY, Roser F, Gregg J, Tse C, Brault D, Lacaine F, Houry S, Huguier M, Franc B, et al: Stage II colon cancer prognosis prediction by tumor gene expression profiling. J Clin Oncol. 2006, 24: 4685-4691. 10.1200/JCO.2005.05.0229.CrossRefPubMed
17.
Eschrich S, Yang I, Bloom G, Kwong KY, Boulware D, Cantor A, Coppola D, Kruhoffer M, Aaltonen L, Orntoft TF, et al: Molecular staging for survival prediction of colorectal cancer patients. J Clin Oncol. 2005, 23: 3526-3535. 10.1200/JCO.2005.00.695.CrossRefPubMed
18.
Koehler A, Bataille F, Schmid C, Ruemmele P, Waldeck A, Blaszyk H, Hartmann A, Hofstaedter F, Dietmaier W: Gene expression profiling of colorectal cancer and metastases divides tumours according to their clinicopathological stage. J Pathol. 2004, 204: 65-74. 10.1002/path.1606.CrossRefPubMed
19.
Lin YH, Friederichs J, Black MA, Mages J, Rosenberg R, Guilford PJ, Phillips V, Thompson-Fawcett M, Kasabov N, Toro T, et al: Multiple gene expression classifiers from different array platforms predict poor prognosis of colorectal cancer. Clin Cancer Res. 2007, 13: 498-507. 10.1158/1078-0432.CCR-05-2734.CrossRefPubMed
20.
Wang Y, Jatkoe T, Zhang Y, Mutch MG, Talantov D, Jiang J, McLeod HL, Atkins D: Gene expression profiles and molecular markers to predict recurrence of Dukes' B colon cancer. J Clin Oncol. 2004, 22: 1564-1571. 10.1200/JCO.2004.08.186.CrossRefPubMed
21.
Smid M, Wang Y, Zhang Y, Sieuwerts AM, Yu J, Klijn JG, Foekens JA, Martens JW: Subtypes of breast cancer show preferential site of relapse. Cancer Res. 2008, 68: 3108-3114. 10.1158/0008-5472.CAN-07-5644.CrossRefPubMed
22.
Smid M, Wang Y, Klijn JG, Sieuwerts AM, Zhang Y, Atkins D, Martens JW, Foekens JA: Genes associated with breast cancer metastatic to bone. J Clin Oncol. 2006, 24: 2261-2267. 10.1200/JCO.2005.03.8802.CrossRefPubMed
23.
Landemaine T, Jackson A, Bellahcene A, Rucci N, Sin S, Abad BM, Sierra A, Boudinet A, Guinebretiere JM, Ricevuto E, et al: A six-gene signature predicting breast cancer lung metastasis. Cancer Res. 2008, 68: 6092-6099. 10.1158/0008-5472.CAN-08-0436.CrossRefPubMed
24.
van Iersel LB, Verlaan MR, Vahrmeijer AL, van Persijn van Meerten EL, Tijl FG, Sparidans RW, Gelderblom H, Kuppen PJ, Tollenaar RA, van de Velde CJ: Hepatic artery infusion of high-dose melphalan at reduced flow during isolated hepatic perfusion for the treatment of colorectal metastases confined to the liver: a clinical and pharmacologic evaluation. Eur J Surg Oncol. 2007, 33: 874-881.CrossRefPubMed
25.
Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, Zoetmulder FA: Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003, 21: 3737-3743. 10.1200/JCO.2003.04.187.CrossRefPubMed
26.
Marinelli A, Vahrmeijer AL, van de Velde CJ: Phase I/II studies of isolated hepatic perfusion with mitomycin C or melphalan in patients with colorectal cancer hepatic metastases. Recent Results Cancer Res. 1998, 147: 83-94.CrossRefPubMed
27.
Joosse SA, van Beers EH, Nederlof PM: Automated array-CGH optimized for archival formalin-fixed, paraffin-embedded tumor material. BMC Cancer. 2007, 7: 43-10.1186/1471-2407-7-43.CrossRefPubMedPubMedCentral
28.
Joosse SA, van Beers EH, Tielen IH, Horlings H, Peterse JL, Hoogerbrugge N, Ligtenberg MJ, Wessels LF, Axwijk P, Verhoef S, et al: Prediction of BRCA1-association in hereditary non-BRCA1/2 breast carcinomas with array-CGH. Breast Cancer Res Treat. 2009, 116: 479-489. 10.1007/s10549-008-0117-z.CrossRefPubMed
29.
van Beers EH, Joosse SA, Ligtenberg MJ, Fles R, Hogervorst FB, Verhoef S, Nederlof PM: A multiplex PCR predictor for aCGH success of FFPE samples. Br J Cancer. 2006, 94: 333-337. 10.1038/sj.bjc.6602889.CrossRefPubMedPubMedCentral
30.
Raap AK, van der Burg MJ, Knijnenburg J, Meershoek E, Rosenberg C, Gray JW, Wiegant J, Hodgson JG, Tanke HJ: Array comparative genomic hybridization with cyanin cis-platinum-labeled DNAs. Biotechniques. 2004, 37: 130-134.PubMed
31.
Klijn C, Holstege H, de Ridder J, Liu X, Reinders M, Jonkers J, Wessels L: Identification of cancer genes using a statistical framework for multiexperiment analysis of nondiscretized array CGH data. Nucleic Acids Res. 2008, 36: e13-10.1093/nar/gkm1143.CrossRefPubMedPubMedCentral
32.
Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D: Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. 1992, 258: 818-821. 10.1126/science.1359641.CrossRefPubMed
33.
Lemmens VE, Klaver YL, Verwaal VJ, Rutten HJ, Coebergh JW, de Hingh IH: Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: A population-based study. Int J Cancer. 2010
34.
Kallioniemi OP, Kallioniemi A, Kurisu W, Thor A, Chen LC, Smith HS, Waldman FM, Pinkel D, Gray JW: ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization. Proc Natl Acad Sci USA. 1992, 89: 5321-5325. 10.1073/pnas.89.12.5321.CrossRefPubMedPubMedCentral
35.
Kallioniemi A, Kallioniemi OP, Citro G, Sauter G, DeVries S, Kerschmann R, Caroll P, Waldman F: Identification of gains and losses of DNA sequences in primary bladder cancer by comparative genomic hybridization. Genes Chromosomes Cancer. 1995, 12: 213-219. 10.1002/gcc.2870120309.CrossRefPubMed
36.
Iwabuchi H, Sakamoto M, Sakunaga H, Ma YY, Carcangiu ML, Pinkel D, Yang-Feng TL, Gray JW: Genetic analysis of benign, low-grade, and high-grade ovarian tumors. Cancer Res. 1995, 55: 6172-6180.PubMed
37.
Fukushige S, Waldman FM, Kimura M, Abe T, Furukawa T, Sunamura M, Kobari M, Horii A: Frequent gain of copy number on the long arm of chromosome 20 in human pancreatic adenocarcinoma. Genes Chromosomes Cancer. 1997, 19: 161-169. 10.1002/(SICI)1098-2264(199707)19:3<161::AID-GCC5>3.0.CO;2-W.CrossRefPubMed
38.
Weiss MM, Snijders AM, Kuipers EJ, Ylstra B, Pinkel D, Meuwissen SG, van Diest PJ, Albertson DG, Meijer GA: Determination of amplicon boundaries at 20q13.2 in tissue samples of human gastric adenocarcinomas by high-resolution microarray comparative genomic hybridization. J Pathol. 2003, 200: 320-326. 10.1002/path.1359.CrossRefPubMed
39.
Postma C, Terwischa S, Hermsen MA, van der Sijp JR, Meijer GA: Gain of chromosome 20q is an indicator of poor prognosis in colorectal cancer. Cell Oncol. 2007, 29: 73-75.PubMedPubMedCentral
40.
Nanashima A, Yamaguchi H, Yasutake T, Sawai T, Kusano H, Tagawa Y, Nakagoe T, Ayabe H: Gain of chromosome 20 is a frequent aberration in liver metastasis of colorectal cancers. Dig Dis Sci. 1997, 42: 1388-1393. 10.1023/A:1018885803931.CrossRefPubMed
41.
Carvalho B, Postma C, Mongera S, Hopmans E, Diskin S, van de Wiel MA, van Criekinge W, Thas O, Matthai A, Cuesta MA, et al: Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression. Gut. 2009, 58: 79-89. 10.1136/gut.2007.143065.CrossRefPubMed
42.
Hermsen M, Postma C, Baak J, Weiss M, Rapallo A, Sciutto A, Roemen G, Arends JW, Williams R, Giaretti W, et al: Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability. Gastroenterology. 2002, 123: 1109-1119. 10.1053/gast.2002.36051.CrossRefPubMed
43.
Knosel T, Schluns K, Stein U, Schwabe H, Schlag PM, Dietel M, Petersen I: Chromosomal alterations during lymphatic and liver metastasis formation of colorectal cancer. Neoplasia. 2004, 6: 23-28.CrossRefPubMedPubMedCentral
44.
Nakao M, Kawauchi S, Furuya T, Uchiyama T, Adachi J, Okada T, Ikemoto K, Oga A, Sasaki K: Identification of DNA copy number aberrations associated with metastases of colorectal cancer using array CGH profiles. Cancer Genet Cytogenet. 2009, 188: 70-76. 10.1016/j.cancergencyto.2008.09.013.CrossRefPubMed
45.
Nakao K, Shibusawa M, Ishihara A, Yoshizawa H, Tsunoda A, Kusano M, Kurose A, Makita T, Sasaki K: Genetic changes in colorectal carcinoma tumors with liver metastases analyzed by comparative genomic hybridization and DNA ploidy. Cancer. 2001, 91: 721-726. 10.1002/1097-0142(20010215)91:4<721::AID-CNCR1057>3.0.CO;2-3.CrossRefPubMed
46.
Hu XT, Chen W, Wang D, Shi QL, Zhang FB, Liao YQ, Jin M, He C: The proteasome subunit PSMA7 located on the 20q13 amplicon is overexpressed and associated with liver metastasis in colorectal cancer. Oncol Rep. 2008, 19: 441-446.PubMed
47.
Rooney PH, Boonsong A, McFadyen MC, McLeod HL, Cassidy J, Curran S, Murray GI: The candidate oncogene ZNF217 is frequently amplified in colon cancer. J Pathol. 2004, 204: 282-288. 10.1002/path.1632.CrossRefPubMed
48.
Cowger JJ, Zhao Q, Isovic M, Torchia J: Biochemical characterization of the zinc-finger protein 217 transcriptional repressor complex: identification of a ZNF217 consensus recognition sequence. Oncogene. 2007, 26: 3378-3386. 10.1038/sj.onc.1210126.CrossRefPubMed
49.
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. 10.1158/0008-5472.CAN-04-0328.CrossRefPubMed
50.
Takahashi Y, Ishii Y, Nishida Y, Ikarashi M, Nagata T, Nakamura T, Yamamori S, Asai S: Detection of aberrations of ubiquitin-conjugating enzyme E2C gene (UBE2C) in advanced colon cancer with liver metastases by DNA microarray and two-color FISH. Cancer Genet Cytogenet. 2006, 168: 30-35. 10.1016/j.cancergencyto.2005.12.011.CrossRefPubMed
51.
Jackson AL, Mao M, Kobayashi S, Ward T, Biery M, Dai H, Bartz SR, Linsley PS: Chromosome 20q amplification regulates in vitro response to Kinesin-5 inhibitor. Cancer Inform. 2008, 6: 147-164.PubMedPubMedCentral
Metadata
Title
Specific genomic aberrations in primary colorectal cancer are associated with liver metastases
Authors
Sjoerd C Bruin
Christiaan Klijn
Gerrit-Jan Liefers
Linde M Braaf
Simon A Joosse
Eric H van Beers
Victor J Verwaal
Hans Morreau
Lodewyk F Wessels
Marie-Louise F van Velthuysen
Rob AEM Tollenaar
Laura J van't Veer
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-10-662

Other articles of this Issue 1/2010

BMC Cancer 1/2010 Go to the issue

Case report

Monozygotic twins with Neurofibromatosis type 1, concordant phenotype and synchronous development of MPNST and metastasis

Research article

Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells

Research article

N-Acetylgalactosaminyltransferase-14 as a potential biomarker for breast cancer by immunohistochemistry

Research article

Epigallocatechin-3-gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo

Research article

Evaluation of immunological escape mechanisms in a mouse model of colorectal liver metastases

Research article

Periostin is up-regulated in high grade and high stage prostate cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits