Skip to main content
SpringerLink
Log in

Analysis of molecular cytogenetic alterations in uterine leiomyosarcoma by array-based comparative genomic hybridization

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Objective

The aim of this study was to identify novel genes following genomic DNA copy number changes using a genome-wide array-based comparative genomic hybridization (array-CGH) analysis in uterine leiomyosarcoma (ULMS).

Methods

Genomic DNA copy number changes were analyzed in 15 cases of ULMS from St Mary’s Hospital of the Catholic University of Korea. The paraffin-fixed tissue samples were micro-dissected under microscope, and DNA was extracted. Array-based CGH and genomic polymerase chain reaction were carried out with statistical analyses such as hierarchical clustering and Gene Ontology.

Results

All of 15 cases of ULMS showed specific gains and losses. The percentage of average gains and losses were 8.4 and 16.6 %, respectively. The analysis limit of average gains and losses was 40 %. The regions of high level of gain were 1q23.3, 7p14.2, 7q34, 7q35, 7q36.3, 13q34, and 16p13.3. And the regions of homozygous loss were 2q21.1, 2q22.1, 2p23.2, 12q23.3, 4q21.22, 4q34.3, 11q24.2, 12q23.3, 13q13.1, 13q21.33, and 14q24.3. In ULMS samples, recurrent regions of gain were 1p36.33, 1p36.32, 5q35.3, 7q36.3, and 8q24.3 and recurrent regions of loss were 1p31.1–p31.3, 1p32.1–p32.3, 2p12, 2p13.3, 2p14, 2p16.2–p16.3, 2q12.1–q12.3, 2q21.1–q21.2, 2q22.2–q22.3, 2q34, 2q36.1–q36.3, 5q21.3, 5q23.3, 5q31.1, 6p11.2, 6p12.1, 10q11.23, 10q21.2–q21.3, 10q23.2, 10q23.31, 10q25.1–q25.2, 10q25.3, 10q26.13, 10q26.2–q26.3, 11p11.2, 11p11.12, 11p12, 11p13, 11p15.4, 11q23.1–q23.2, 11q23.3, 13q14.12, 13q14.13–13q14.2, 13q14.2, 13q14.2, 13q14.3, 13q21.33, 13q22.1–q22.3, 14q24.2, 14q24.3, 14q31.1, 14q32.33, 15q11.2–q13, 15q14, 16q22.3, 16q23.1, 16q23.2, 16q24.1, 20p12.1, and 21q22.3. Representative frequently gained BAC clones encoded genes were HDAC9, CRR9, SOX18, PTPRN2, SKI, SOLH, and KIAA1199. The genes encoded by frequently lost BAC clones were LOC150516 and AMY2A. A subset of cellular processes from each gene were clustered by Gene Ontology database.

Conclusions

The present study using array-CGH analyses sought a deeper elucidation of the specific genomic alterations related to ULMS. The high resolution of array-CGH combined with human genome database would give a chance at identifying relevant target genes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Albertson DG, Ylstra B, Segraves R, Collins C, Dairkee SH, Kowbel D, Kuo WL, Gray JW, Pinkel D (2000) Quantitative mapping of amplicon structure by array CGH identifies CYP24 as a candidate oncogene. Nat Genet 25:144–146

    Article  PubMed  CAS  Google Scholar 

  • Ashar HR, Fejzo MS, Tkachenko A, Zhou X, Fletcher JA, Weremowicz S, Morton CC, Chada K (1995) Disruption of the architectural factor HMGI-C: DNA-binding AT hook motifs fused in lipomas to distinct transcriptional regulatory domains. Cell 82:57–65

    Article  PubMed  CAS  Google Scholar 

  • Barbieri RL, Andersen JA (1992) Uterine leiomyomas: the somatic mutation theory. Semin Reprod Endocrinol 10:301–309

    Article  Google Scholar 

  • Boghosian L, Dal Cin P, Turc-Carel C, Rao U, Karakousis C, Sait SJ, Sandberg AA (1989) Three possible cytogenetic subgroups of leiomyosarcoma. Cancer Genet Cytogenet 43:39–49

    Article  PubMed  CAS  Google Scholar 

  • Cho YL, Bae S, Koo MS, Kim KM, Chun HJ, Kim CK, Ro DY, Kim JH, Lee CH, Kim YW, Ahn WS (2005) Array comparative genomic hybridization analysis of uterine leiomyosarcoma. Gynecol Oncol 99:545–551

    Article  PubMed  CAS  Google Scholar 

  • Dei Tos AP, Maestro R, Doglioni C, Piccinin S, Libera DD, Boiocchi M, Fletcher CD (1996) Tumor suppressor genes and related molecules in leiomyosarcoma. Am J Pathol 148:1037–1045

    PubMed  CAS  Google Scholar 

  • El-Rifai W, Sarlomo-Rikala M, Knuutila S, Miettinen M (1998) DNA copy number changes in development and progression in leiomyosarcomas of soft tissues. Am J Pathol 153:985–990

    Article  PubMed  CAS  Google Scholar 

  • Gibas Z, Griffin CA, Emanuel BS (1988) Clonal chromosome rearrangements in a uterine myoma. Cancer Genet Cytogenet 32:19–24

    Article  PubMed  CAS  Google Scholar 

  • Hamlin C, Finkler NJ (1992) Uterine myomas and cancer. Sem Reprod Endocrinol 10:339–343

    Article  Google Scholar 

  • Hsu LS, Lee HC, Chau GY, Yin PH, Chi CW, Lui WY (2006) Aberrant methylation of EDNRB and p16 genes in hepatocellular carcinoma (HCC) in Taiwan. Oncol Rep 15:507–511

    PubMed  CAS  Google Scholar 

  • Hu J, Khanna V, Jones M, Surti U (2001) Genomic alterations in uterine leiomyosarcomas: potential markers for clinical diagnosis and prognosis. Genes Chromosom Cancer 31:117–124

    Article  PubMed  CAS  Google Scholar 

  • Knuutila S, Bjorkqvist AM, Autio K, Tarkkanen M, Wolf M, Monni O, Szymanska J, Larramendy ML, Tapper J, Pere H, El-Rifai W, Hemmer S, Wasenius VM, Vidgren V, Zhu Y (1998) DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies. Am J Pathol 152:1107–1123

    PubMed  CAS  Google Scholar 

  • Krzywinski M, Bosdet I, Smailus D, Chiu R, Mathewson C, Wye N, Barber S, Brown-John M, Chan S, Chand S, Cloutier A, Girn N, Lee D, Masson A, Mayo M, Olson T, Pandoh P, Prabhu AL, Schoenmakers E, Tsai M, Albertson D, Lam W, Choy CO, Osoegawa K, Zhao S, de Jong PJ, Schein J, Jones S, Marra MA (2004) A set of BAC clones spanning the human genome. Nucleic Acids Res 32:3651–3660

    Article  PubMed  CAS  Google Scholar 

  • Levy B, Mukherjee T, Hirschhorn K (2000) Molecular cytogenetic analysis of uterine leiomyoma and leiomyosarcoma by comparative genomic hybridization. Cancer Genet Cytogenet 121:1–8

    Article  PubMed  CAS  Google Scholar 

  • Li J, Jiang T, Mao JH, Balmain A, Peterson L, Harris C, Rao PH, Havlak P, Gibbs R, Cai WW (2004) Genomic segmental polymorphisms in inbred mouse strains. Nat Genet 36:952–954

    Article  PubMed  CAS  Google Scholar 

  • Mark J, Havel G, Grepp C, Dahlenfors R, Wedell B (1988) Cytogenetical observations in human benign uterine leiomyomas. Anticancer Res 8:621–626

    PubMed  CAS  Google Scholar 

  • Mittal K, Demopoulos RI (2001) MIB-1 (Ki-67), p53, estrogen receptor, and progesterone receptor expression in uterine smooth muscle tumors. Hum Pathol 32:984–987

    Article  PubMed  CAS  Google Scholar 

  • Morton CC (1998) Warner-Lambert/Parke-Davis Award lecture. Many tumors and many genes: genetics of uterine leiomyomata. Am J Pathol 153:1015–1020

    Article  PubMed  CAS  Google Scholar 

  • Packenham JP, du Manoir S, Schrock E, Risinger JI, Dixon D, Denz DN, Evans JA, Berchuck A, Barrett JC, Devereux TR, Ried T (1997) Analysis of genetic alterations in uterine leiomyomas and leiomyosarcomas by comparative genomic hybridization. Mol Carcinog 19:273–279

    Article  PubMed  CAS  Google Scholar 

  • Pinkel D, Segraves R, Sudar D, Clark S, Poole I, Kowbel D, Collins C, Kuo WL, Chen C, Zhai Y, Dairkee SH, Ljung BM, Gray JW, Albertson DG (1998) High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet 20:207–211

    Article  PubMed  CAS  Google Scholar 

  • Pollack JR, Perou CM, Alizadeh AA, Eisen MB, Pergamenschikov A, Williams CF, Jeffrey SS, Botstein D, Brown PO (1999) Genome-wide analysis of DNA copy-number changes using cDNA microarrays. Nat Genet 23:41–46

    Article  PubMed  CAS  Google Scholar 

  • Quade BJ, Pinto AP, Howard DR, Peters WA 3rd, Crum CP (1999) Frequent loss of heterozygosity for chromosome 10 in uterine leiomyosarcoma in contrast to leiomyoma. Am J Pathol 154:945–950

    Article  PubMed  CAS  Google Scholar 

  • Sait SN, Dal Cin P, Sandberg AA (1988) Consistent chromosome changes in leiomyosarcoma. Cancer Genet Cytogenet 35:47–50

    Article  PubMed  CAS  Google Scholar 

  • Schoenmakers EF, Wanschura S, Mols R, Bullerdiek J, Van den Berghe H, Van de Ven WJ (1995) Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours. Nat Genet 10:436–444

    Article  PubMed  CAS  Google Scholar 

  • Solinas-Toldo S, Lampel S, Stilgenbauer S, Nickolenko J, Benner A, Dohner H, Cremer T, Lichter P (1997) Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosom Cancer 20:399–407

    Article  PubMed  CAS  Google Scholar 

  • Sreekantaiah C, Davis JR, Sandberg AA (1993) Chromosomal abnormalities in leiomyosarcomas. Am J Pathol 142:293–305

    PubMed  CAS  Google Scholar 

  • Tagawa H, Tsuzuki S, Suzuki R, Karnan S, Ota A, Kameoka Y, Suguro M, Matsuo K, Yamaguchi M, Okamoto M, Morishima Y, Nakamura S, Seto M (2004) Genome-wide array-based comparative genomic hybridization of diffuse large B-cell lymphoma: comparison between CD5-positive and CD5-negative cases. Cancer Res 64:5948–5955

    Article  PubMed  CAS  Google Scholar 

  • Tsibris JC, Segars J, Coppola D, Mane S, Wilbanks GD, O’Brien WF, Spellacy WN (2002) Insights from gene arrays on the development and growth regulation of uterine leiomyomata. Fertil Steril 78:114–121

    Article  PubMed  Google Scholar 

  • Walker CL, Stewart EA (2005) Uterine fibroids: the elephant in the room. Science 308:1589–1592

    Article  PubMed  CAS  Google Scholar 

  • Wechsler DS, Shelly CA, Dang CV (1996) Genomic organization of human MXI1, a putative tumor suppressor gene. Genomics 32:466–470

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

    Mohammad Raish, Mohsin Khurshid & Mushtaq Ahmad Ansari

  2. Catholic Research Institutes of Medical Science, The Catholic University of Korea, 505 Banpodong, Seocho-ku, Seoul, 137-701, Republic of Korea

    Mohammad Raish, Pankaj Kumar Chaturvedi, Su-Mi Bae & Woong Shick Ahn

  3. Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Republic of Korea

    Jang Heub Kim, Eun Kyung Park, Dong Chun Park & Woong Shick Ahn

Authors
  1. Mohammad Raish
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohsin Khurshid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mushtaq Ahmad Ansari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pankaj Kumar Chaturvedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Su-Mi Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jang Heub Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eun Kyung Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dong Chun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Woong Shick Ahn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Woong Shick Ahn.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Raish, M., Khurshid, M., Ansari, M.A. et al. Analysis of molecular cytogenetic alterations in uterine leiomyosarcoma by array-based comparative genomic hybridization. J Cancer Res Clin Oncol 138, 1173–1186 (2012). https://doi.org/10.1007/s00432-012-1182-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-012-1182-6

Keywords

Search

Navigation