Clinical & Experimental Metastasis

, Volume 22, Issue 7, pp 533–538 | Cite as

Chromosomal Alterations in Lung Metastases of Colorectal Carcinomas: Associations with Tissue Specific Tumor Dissemination

  • Thomas Knösel
  • Karsten Schlüns
  • Manfred Dietel
  • Iver Petersen


Comparative genomic hybridization was used to screen colorectal carcinomas for chromosomal aberrations that are associated with the metastatic phenotype of the lung. Specimens of 13 lung metastases, 6 primary tumors, 1 lymph node metastasis, 1 liver metastasis, and 1 ovarian metastasis were investigated and added to our CGH colon cancer tumor collective, comprising 85 tumor specimens from 56 patients (see CGH online tumor database at Lung metastases showed more alterations than liver metastases, particularly more deletions at 1p, 3p, 9q, 12q, 17q, 19p and 22q and gains at 2q, 5p, and chromosome 6. Comparing lung metastases with their corresponding primary tumors, particularly more deletions at 3p, 8p, 12q, 17q, and 21q21 and gains at 5p were observed. Based on our results, we wish to suggest a metastatic progression model. Specific subpopulations of metastatic cells have a distinct metastatic potential, which is reflected by a non-random accumulation of chromosomal alterations. Distinct alterations already exist within the primary tumor and this “ready to go package” gives the cells the metastatic potential to achieve the complex series of events needed for metastasis.


CGH colorectal cancer liver metastases lung metastases metastasis 


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  1. 1.
    Saltz, LB, Cox, JV, Blanke, C,  et al. 2000Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study GroupN Engl J Med34390514CrossRefPubMedGoogle Scholar
  2. 2.
    Andre, T, Boni, C, Mounedji-Boudiaf, L,  et al. 2004Multicenter international study of oxaliplatin/5 fluorouracil/leucovorin in the adjuvant treatment of colon cancer (MOSAIC) investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancerN Engl J Med350234351CrossRefPubMedGoogle Scholar
  3. 3.
    Radinsky, R, Risin, S, Fan, D,  et al. 1995Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cellsClin Cancer Res11931PubMedGoogle Scholar
  4. 4.
    Italiano, A, Saint-Paul, MC, Caroli-Bosc, FX,  et al. 2005Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implicationsAnn Oncol1615037CrossRefPubMedGoogle Scholar
  5. 5.
    Knösel, T, Petersen, S, Schwabe, H,  et al. 2002Incidence of chromosomal imbalances in advanced colorectal carcinomas and their metastasesVirchows Arch44018794PubMedGoogle Scholar
  6. 6.
    Petersen, I,  et al. 2003Comparative genomic hybridization of human lung cancerMethods Mol Med7520937PubMedGoogle Scholar
  7. 7.
    Knösel, T, Schlüns, K, Stein, U,  et al. 2004Chromosomal alterations during lymphatic and liver metastasis formation of colorectal cancerNeoplasia6238PubMedGoogle Scholar
  8. 8.
    Petersen, I, Bujard, M, Petersen, S,  et al. 1997Patterns of chromosomal imbalances in adenocarcinoma and squamous cell carcinoma of the lungCancer Res5723315PubMedGoogle Scholar
  9. 9.
    Fearon, ER, Vogelstein, B,  et al. 1990A genetic model for colorectal tumourigenesisCell6175967CrossRefPubMedGoogle Scholar
  10. 10.
    Knösel, T, Schlüns, K, Stein, U,  et al. 2003Genetic imbalances with impact on survival in colorectal cancer patientsHistopathology4332331PubMedGoogle Scholar
  11. 11.
    Gerdes, H, Chen, Q, Elahi, AH,  et al. 1995Recurrent deletions involving chromosomes 1, 5, 17, and 18 in colorectal carcinoma: possible role in biological and clinical behavior of tumorsAnticancer Res151324PubMedGoogle Scholar
  12. 12.
    Ogunbiyi, OA, Goodfellow, PJ, Gagliardi, G,  et al. 1997Prognostic value of chromosome 1p allelic loss in colon cancerGastroenterology1137616CrossRefPubMedGoogle Scholar
  13. 13.
    Diep, CB, Parada, LA, Teixeira, MR,  et al. 2003Genetic profiling of colorectal cancer liver metastases by combined comparative genomic hybridization and G-banding analysisGenes Chromosomes Cancer3618997CrossRefPubMedGoogle Scholar
  14. 14.
    Bockmühl, U, Schlüns, K, Küchler, I,  et al. 2000Genetic imbalances with impact on survival in head and neck cancer patientsAm J Pathol15736975PubMedGoogle Scholar
  15. 15.
    Palanisamy, N, Abou-Elella, AA, Chaganti, SR,  et al. 2002Similar patterns of genomic alterations characterize primary mediastinal large-B-cell lymphoma and diffuse large-B-cellGenes Chromosomes Cancer3311422CrossRefPubMedGoogle Scholar
  16. 16.
    Schwirzke, M, Schiemann, S, Gnirke, A,  et al. 1999New genes potentially involved in breast cancer metastasisAnticancer Res19180114PubMedGoogle Scholar
  17. 17.
    Knösel, T, Yu, Y, Stein, U,  et al. 2004Overexpression of Cyclooxygenase-2 correlates with chromosomal gain at the Cyclooxygenase-2 locus and decreased patients survival in advanced colorectal carcinomasDis Colon Rectum47707CrossRefPubMedGoogle Scholar
  18. 18.
    Agathanggelou, A, Dallol, A, Zochbauer-Muller, S,  et al. 2003Epigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancersOncogene2215808CrossRefPubMedGoogle Scholar
  19. 19.
    Cairns, P, Polascik, TJ, Eby, Y,  et al. 1995Frequency of homozygous deletion at p16/CDKN2 in primary human tumoursNat Genet112102CrossRefPubMedGoogle Scholar
  20. 20.
    Schmid, M, Sen, M, Rosenbach, MD,  et al. 2000A methylthioadenosine phosphorylase (MTAP) fusion transcript identifies a new gene on chromosome 9p21 that is frequently deleted in cancerOncogene19574754CrossRefPubMedGoogle Scholar
  21. 21.
    Steeg, PS,  et al. 2003Metastasis suppressors alter the signal transduction of cancer cellsNat Rev Cancer3 5563CrossRefPubMedGoogle Scholar
  22. 22.
    Jiang, JK, Chen, YJ, Lin, CH,  et al. 2005Genetic changes and clonality relationship between primary colorectal cancers and their pulmonary metastases – an analysis by comparative genomic hybridizationGenes Chromosomes Cancer432536CrossRefPubMedGoogle Scholar
  23. 23.
    Paget, S 1989The distribution of secondary growths in cancer of the breast. 1889Cancer Metast Rev298101Google Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  • Thomas Knösel
    • 1
  • Karsten Schlüns
    • 1
    • 2
  • Manfred Dietel
    • 1
  • Iver Petersen
    • 1
    • 3
  1. 1.Institute of PathologyBerlinGermany
  2. 2.Digital Pathology and ITInstitute of PathologyBerlinGermany
  3. 3.Institute of PathologyUniversity Hospital CharitéBerlinGermany

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