Whole Genome Microarray Analysis In Invasive Ductal Breast Cancer Revealed The Most Significant Changes Affect Chromosomes 1, 8, 17 And 20

Whole Genome Microarray Analysis In Invasive Ductal Breast Cancer Revealed The Most Significant Changes Affect Chromosomes 1, 8, 17 And 20

Loading document ...
Page
of
Loading page ...

Author(s)

Author(s): Ivanka Dimova, Radka Tafradzhiska-Hadzhiolova, Svilen Maslyankov, Desislava Nesheva, Draga Toncheva

Download Full PDF Read Complete Article

349 924 8-17 Volume 4 - Jan 2015

Abstract

Despite of the large number of molecular studies in breast cancer, the data are still insufficient for understanding its molecular pathogenesis. The dramatic development of genetics in recent years has made it possible to gain insight into the molecular mechanisms of tumorigenesis. The aims of the study was to determine the type, frequency and fine mapping of unbalanced genomic alterations in ductal carcinoma of the breast. For this study we have used tumor samples of invasive ductal breast cancer to be analysed by comparative genomic hybridization on DNA microarrays. Two approaches were applied in the analysis of significant unbalanced genomic changes: a) identification of clones which presented unbalanced changes (log2 T: H> +0.25 for gain and <-0.25 for losses) in more than 70% of the tumors; b) establishing clones which harbor amplifications (log2 T: H> +0.5) or homozygous deletions (log2 T: H <- 0.5) in more than 50% of tumors. Our results showed that the most commonly affected chromosome arms by gains were 20q and 1q. Loss at high frequency was found in 8p. Totally 9 regions with high rate of genetic alterations (7 in short and 2 in long arm) were detected in chromosome 1. Genetic losses in chromosome 8 predominated - 8p11.21 have lost in 100% of the cases. There were regions of chromosome 17 with a frequency of genetic gains over 70% - in 17q12, 17q21.31, 17q22 and a region with a frequency of more than 80% loss in 17q21.32. The long arm of chromosome 20 was affected by significant amplifications in 10 regions, but with the highest frequency of more than 80% in 20q11.21-q11.23, 20q12 and 20q13.12-q13.2. Our study contributed to the fine mapping of genomic imbalances in ductal breast cancer, suggesting the significant regions of genetic gains and losses. The genes in the found regions could represent potential oncogenes and/or tumor-supressor genes with cancer-emerging role.

Keywords

ductal breast cancer, array CGH, oncogenes and tumor-supressor genes

References

  1. Berchuck A, Kohler M, Bast R Oncogenes in ovarian cancer. Hematol Oncol (1992) 4:813-827
  2. www.atlasgeneticsoncology.org/Tumors/breastID5018.html
  3. Bieche I and Lidereau R. Genetic alterations in breast cancer. Genes Chromosom Cancer 1995; 14: 227-251
  4. Heim S and Mitelman F. Tumors of the breast. Cancer Cytogenetics, Wiley-Liss, 1995.Bernardino J, Apiou F, Gerbault-Seureau M, Malfoy B, Dutrillaux B. Characterization of recurrent homogeneously staining regions in 72 breast carcinomas. Genes Chromosom Cancer 1998; 23: 100-108
  5. Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan X-Y, Sauter G, Kallioniemi O-P, Trent JM, Meltzer PS. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 1997; 277: 965-968
  6. Loo L, Grove D, Williams E et al. Array comparative genomic hybridization analysis of genomic alterations in breast cancer subtypes. Cancer Res 2004, 64: 8541-8549.
  7. Fritz B, Schubert F, wrobel G et al. Microarray-based copy number and expression profiling in dedifferentiated and pleomorphic liposarcoma. Cancer Res 2002, 62: 2993-2998
  8. Van Dekken H, Paris PL, Albertson DG et al. Evaluation of genetic patterns in different tumor arreas of intermediate-grade prostatic adenocarcinomas by high-resolution genomic array analysis. Genes Chromosomes Cnacer 2004, 39 (3): 249-56.
  9. Jones AM, Douglas EJ, Halford SE et al. Array-CGH analysis of microsatellite-stable, near diploid bowel cancers and comparison with other types of colorectal carcinoma. Oncogene 2005, 24 (1): 118-29
  10. Douglas E, Fiegler H, Rowan A, et al. Array comparative genomic hybridization analysis of colorectal cancer cell lines and primary carcinomas. Cancer Res 2004, 64: 4817-25.
  11. Wessendorf S, Nessling M, Moller P, et al. Hidden gene amplifications in aggressive B-cell non-Hodgkin lymphomas detected by microarray-based comparative genomic hybridization. Oncogene 2003, 22: 1425-1429
  12. Albertson DG, Yistra B, Segraves R, et al. Quantitative mapping of amplicon structure by array CGH identifies CYP24 as a candidate oncogene. Nat genet 2000, 25:144-146
  13. Monni O, Barlund M, Mousses S, et al. Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer. Proc Natl Acad Sci 2001, 98: 5711-16
  14. Rennstam K, Ahlstedt-Soini M, Baldetorp B, Bendahl PO, Borg A, Karhu R, Tanner M, Tirkkonen M, Isola J: Patterns of chromosomal imbalances defines subgroups of breast cancer with distinct clinical features and prognosis. A study of 305 tumors by comparative genomic hybridization. Cancer Res 2003, 63:8861-8868
  15. Pollack JR, Perou CM, Alizadeh AA, Eisen MB, Pergamenschikov A, Williams CF, Jeffrey SS, Botstein D, Brown PO: Genome-wide analysis of DNA copy-number changes using cDNA microarrays. Nat Genet 1999, 23:41-46
  16. Pollack JR, Sorlie T, Perou CM, Rees CA, Jeffrey SS, Lonning PE, Tibshirani R, Botstein D, Borresen-Dale AL, Brown PO: Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors. Proc Natl Acad Sci USA 2002, 99:12963-12968
  17. Albertson DG: Profiling breast cancer by array CGH. Breast Cancer Res Treat 2003, 78:289-298
  18. Tirkkonen M, Tanner M, Karhu R, Kallioniemi A, Isola J, Kallioniemi OP: Molecular cytogenetics of primary breast cancer by CGH. Genes Chromosomes Cancer 1998, 21:177-184
  19. Orsetti B, Nugoli M, Cervera N, Lasorsa L, Chuchana P, Rougé C, Ursule L, Nguyen C, Bibeau F, Rodriguez C, Theillet C. Genetic profiling of chromosome 1 in breast cancer: mapping of regions of gains and losses and identification of candidate genes on 1q. Br J Cancer. 2006 Nov 20;95(10):1439-47
  20. Rodriguez V, Chen Y, Elkahloun A, Dutra A, Pak E, Chandrasekharappa S. Chromosome 8 BAC array comparative genomic hybridization and expression analysis identify amplification and overexpression of TRMT12 in breast cancer. Genes Chromosomes Cancer. 2007 Jul;46(7):694-707
  21. Orsetti B, Nugoli M, Cervera N, Lasorsa L, Chuchana P, Ursule L, Nguyen C, Redon R, du Manoir St, Rodriguez C, Theillet C. Genomic and expression profiling of chromosome 17 in breast cancer reveals complex catterns of alterations and novel candidate genes. Cancer Research 64, 6453-6460, September 15, 2004
  22. Hodgson JG, Chin K, Collins C, Gray JW. Genome amplification of chromosome 20 in breast cancer. Breast Cancer Res Treat. 2003;78:337–345
  23. Collins C, Volik S, Kowbel D, Ginzinger D, Ylstra B, Cloutier T, Hawkins T, Predki P, Martin C, Wernick M, et al. Comprehensive genome sequence analysis of a breast cancer amplicon. Genome Res. 2001;11:1034–1042

Cite this Article:

  • BibTex
  • RIS
  • APA
  • Harvard
  • IEEE
  • MLA
  • Vancouver
  • Chicago

International Journal of Sciences is Open Access Journal.
This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.
Author(s) retain the copyrights of this article, though, publication rights are with Alkhaer Publications.

Search Articles

Issue June 2019

Volume 8, June 2019


Table of Contents


Order Print Copy

World-wide Delivery is FREE

Share this Issue with Friends:


Submit your Paper