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

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Abstract

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 http://amba.charite.de/cgh). 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.

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References

  1. LB Saltz JV Cox C Blanke et al. (2000) ArticleTitleIrinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group N Engl J Med 343 IssueID13 905–14 Occurrence Handle10.1056/NEJM200009283431302 Occurrence Handle1:CAS:528:DC%2BD3cXntFOkt7Y%3D Occurrence Handle11006366

    Article  CAS  PubMed  Google Scholar 

  2. T Andre C Boni L Mounedji-Boudiaf et al. (2004) ArticleTitleMulticenter 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 cancer N Engl J Med 350 IssueID23 2343–51 Occurrence Handle10.1056/NEJMoa032709 Occurrence Handle1:CAS:528:DC%2BD2cXks1Gjt78%3D Occurrence Handle15175436

    Article  CAS  PubMed  Google Scholar 

  3. R Radinsky S Risin D Fan et al. (1995) ArticleTitleLevel and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells Clin Cancer Res 1 IssueID1 19–31 Occurrence Handle1:CAS:528:DyaK2MXlvVaku7c%3D Occurrence Handle9815883

    CAS  PubMed  Google Scholar 

  4. A Italiano MC Saint-Paul FX Caroli-Bosc et al. (2005) ArticleTitleEpidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implications Ann Oncol 16 IssueID9 1503–7 Occurrence Handle10.1093/annonc/mdi282 Occurrence Handle1:STN:280:DC%2BD2MrjtlGhtg%3D%3D Occurrence Handle15980160

    Article  CAS  PubMed  Google Scholar 

  5. T Knösel S Petersen H Schwabe et al. (2002) ArticleTitleIncidence of chromosomal imbalances in advanced colorectal carcinomas and their metastases Virchows Arch 440 187–94 Occurrence Handle11964050

    PubMed  Google Scholar 

  6. I Petersen et al. (2003) ArticleTitleComparative genomic hybridization of human lung cancer Methods Mol Med 75 209–37 Occurrence Handle1:CAS:528:DC%2BD38XovVWksrs%3D Occurrence Handle12407743

    CAS  PubMed  Google Scholar 

  7. T Knösel K Schlüns U Stein et al. (2004) ArticleTitleChromosomal alterations during lymphatic and liver metastasis formation of colorectal cancer Neoplasia 6 IssueID1 23–8 Occurrence Handle15068668

    PubMed  Google Scholar 

  8. I Petersen M Bujard S Petersen et al. (1997) ArticleTitlePatterns of chromosomal imbalances in adenocarcinoma and squamous cell carcinoma of the lung Cancer Res 57 IssueID12 2331–5 Occurrence Handle1:CAS:528:DyaK2sXjvFKitrc%3D Occurrence Handle9192802

    CAS  PubMed  Google Scholar 

  9. ER Fearon B Vogelstein et al. (1990) ArticleTitleA genetic model for colorectal tumourigenesis Cell 61 759–67 Occurrence Handle10.1016/0092-8674(90)90186-I Occurrence Handle1:CAS:528:DyaK3cXktlyhtrg%3D Occurrence Handle2188735

    Article  CAS  PubMed  Google Scholar 

  10. T Knösel K Schlüns U Stein et al. (2003) ArticleTitleGenetic imbalances with impact on survival in colorectal cancer patients Histopathology 43 IssueID4 323–31 Occurrence Handle14511250

    PubMed  Google Scholar 

  11. H Gerdes Q Chen AH Elahi et al. (1995) ArticleTitleRecurrent deletions involving chromosomes 1, 5, 17, and 18 in colorectal carcinoma: possible role in biological and clinical behavior of tumors Anticancer Res 15 13–24 Occurrence Handle1:CAS:528:DyaK2MXmt1Gnsb0%3D Occurrence Handle7733622

    CAS  PubMed  Google Scholar 

  12. OA Ogunbiyi PJ Goodfellow G Gagliardi et al. (1997) ArticleTitlePrognostic value of chromosome 1p allelic loss in colon cancer Gastroenterology 113 761–6 Occurrence Handle10.1016/S0016-5085(97)70169-0 Occurrence Handle1:STN:280:ByiH3svgvVQ%3D Occurrence Handle9287966

    Article  CAS  PubMed  Google Scholar 

  13. CB Diep LA Parada MR Teixeira et al. (2003) ArticleTitleGenetic profiling of colorectal cancer liver metastases by combined comparative genomic hybridization and G-banding analysis Genes Chromosomes Cancer 36 189–97 Occurrence Handle10.1002/gcc.10162 Occurrence Handle1:CAS:528:DC%2BD3sXhtlKmt7k%3D Occurrence Handle12508247

    Article  CAS  PubMed  Google Scholar 

  14. U Bockmühl K Schlüns I Küchler et al. (2000) ArticleTitleGenetic imbalances with impact on survival in head and neck cancer patients Am J Pathol 157 369–75 Occurrence Handle10934141

    PubMed  Google Scholar 

  15. N Palanisamy AA Abou-Elella SR Chaganti et al. (2002) ArticleTitleSimilar patterns of genomic alterations characterize primary mediastinal large-B-cell lymphoma and diffuse large-B-cell Genes Chromosomes Cancer 33 114–22 Occurrence Handle10.1002/gcc.10016 Occurrence Handle1:CAS:528:DC%2BD38XntFWnug%3D%3D Occurrence Handle11793437

    Article  CAS  PubMed  Google Scholar 

  16. M Schwirzke S Schiemann A Gnirke et al. (1999) ArticleTitleNew genes potentially involved in breast cancer metastasis Anticancer Res 19 1801–14 Occurrence Handle1:CAS:528:DyaK1MXmsFCltL0%3D Occurrence Handle10470119

    CAS  PubMed  Google Scholar 

  17. T Knösel Y Yu U Stein et al. (2004) ArticleTitleOverexpression of Cyclooxygenase-2 correlates with chromosomal gain at the Cyclooxygenase-2 locus and decreased patients survival in advanced colorectal carcinomas Dis Colon Rectum 47 IssueID1 70–7 Occurrence Handle10.1007/s10350-003-0008-7 Occurrence Handle14719154

    Article  PubMed  Google Scholar 

  18. A Agathanggelou A Dallol S Zochbauer-Muller et al. (2003) ArticleTitleEpigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers Oncogene 22 1580–8 Occurrence Handle10.1038/sj.onc.1206243 Occurrence Handle1:CAS:528:DC%2BD3sXhvFShur8%3D Occurrence Handle12629521

    Article  CAS  PubMed  Google Scholar 

  19. P Cairns TJ Polascik Y Eby et al. (1995) ArticleTitleFrequency of homozygous deletion at p16/CDKN2 in primary human tumours Nat Genet 11 210–2 Occurrence Handle10.1038/ng1095-210 Occurrence Handle1:CAS:528:DyaK2MXosF2rt70%3D Occurrence Handle7550353

    Article  CAS  PubMed  Google Scholar 

  20. M Schmid M Sen MD Rosenbach et al. (2000) ArticleTitleA methylthioadenosine phosphorylase (MTAP) fusion transcript identifies a new gene on chromosome 9p21 that is frequently deleted in cancer Oncogene 19 5747–54 Occurrence Handle10.1038/sj.onc.1203942 Occurrence Handle1:CAS:528:DC%2BD3cXoslylsLc%3D Occurrence Handle11126361

    Article  CAS  PubMed  Google Scholar 

  21. PS Steeg et al. (2003) ArticleTitleMetastasis suppressors alter the signal transduction of cancer cells Nat Rev Cancer 3 IssueID1 55–63 Occurrence Handle10.1038/nrc967 Occurrence Handle1:CAS:528:DC%2BD38XpvVertbw%3D Occurrence Handle12509767

    Article  CAS  PubMed  Google Scholar 

  22. JK Jiang YJ Chen CH Lin et al. (2005) ArticleTitleGenetic changes and clonality relationship between primary colorectal cancers and their pulmonary metastases – an analysis by comparative genomic hybridization Genes Chromosomes Cancer 43 IssueID1 25–36 Occurrence Handle10.1002/gcc.20167 Occurrence Handle1:CAS:528:DC%2BD2MXjt1Kqsbs%3D Occurrence Handle15723340

    Article  CAS  PubMed  Google Scholar 

  23. S Paget (1989) ArticleTitleThe distribution of secondary growths in cancer of the breast. 1889 Cancer Metast Rev 2 98–101

    Google Scholar 

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Correspondence to Iver Petersen.

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Knösel, T., Schlüns, K., Dietel, M. et al. Chromosomal Alterations in Lung Metastases of Colorectal Carcinomas: Associations with Tissue Specific Tumor Dissemination. Clin Exp Metastasis 22, 533–538 (2005). https://doi.org/10.1007/s10585-005-5239-7

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  • DOI: https://doi.org/10.1007/s10585-005-5239-7

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