Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Oncogenomics
  • Published:

Deletion mapping using quantitative real-time PCR identifies two distinct 3p21.3 regions affected in most cervical carcinomas

Oncogene volume 22, pages 2984–2992 (2003)Cite this article

Abstract

We report chromosome 3p deletion mapping of 32 cervical carcinoma (CC) biopsies using 26 microsatellite markers located in frequently deleted 3p regions to detect loss of heterozygosity and homozygous loss. In addition, two STS markers (NLJ-003 and NL3-001) located in the 3p21.3 telomeric (3p21.3T) and 3p21.3 centromeric (3p21.3C) regions, respectively, were used for quantitative real-time PCR as TaqMan probes. We show that quantitative real-time PCR is reliable and sensitive and allows discriminating between 0, 1 and 2 marker copies per human genome. For the first time, frequent (five of 32 cases, i.e. 15.6%) homozygous deletions were demonstrated in CCs in both 3p21.3T and 3p21.3C regions. The smallest region homozygously deleted in 3p21.3C was located between D3S1568 (CACNA2D2 gene) and D3S4604 (SEMA3F gene) and contains 17 genes previously defined as lung cancer candidate Tumor suppressor genes (TSG(s)). The smallest region homozygously deleted in 3p21.3T was flanked by D3S1298 and NL1-024 (D3S4285), excluding DLEC1 and MYD88 as candidate TSGs involved in cervical carcinogenesis. Overall, this region contains five potential candidates, namely GOLGA4, APRG1, ITGA9, HYA22 and VILL, which need to be analysed. The data showed that aberrations of either NLJ-003 or NL3-001 were detected in 29 cases (90.6%) and most likely have a synergistic effect (P<0.01). The study also demonstrated that aberrations in 3p21.3 were complex and in addition to deletions, may involve gene amplification as well. The results strongly suggest that 3p21.3T and 3p21.3C regions harbor genes involved in the origin and/or development of CCs and imply that those genes might be multiple TSG(s).

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

Abbreviations

CC:

cervical carcinoma

CGH:

comparative genome hybridization

GDB:

genome data base

H allele:

high-molecular-weight allele

ACTB :

human β-actin gene

L allele:

low-molecular-weight allele

LDB:

location database

LOH:

loss of heterozygosity

NSCLC:

non-small cell lung carcinoma

PF2K :

phospho-fructo-2 kinase gene

RCC:

renal cell carcinoma

STS:

sequence-tagged site

SCLC:

small cell lung carcinoma

TSG:

tumor suppressor gene

References

  • Acevedo CM, Henriquez M, Emmert-Buck M and Chuaqui RF . (2002). Cancer, 94, 793–802.

  • Alimov A, Kost-Alimova M, Liu J, Li C, Bergerheim U, Imreh S, Klein G and Zabarovsky ER . (2000). Oncogene, 19, 1392–1399.

  • Angeloni D and Lerman MI (2001). Human Lung cancer: Cancer-Causing Genes, Environmental Factors. Sourcebook on Asbestos Diseases, Vol. 23. Peters GA, Peters BJ (eds). Philadelphia: LexisNexis Press, pp 169–209.

  • Baylin SB and Herman JG . (2000). Trends Genet., 16, 168–174.

  • Boulay J-L, Reuter J, Ristchard R, Terracciano L, Herrmann R and Rochlist C . (1999). BioTechniques, 27, 228–232.

  • Braga EA, Kotova EI, Pugacheva EM, Gizatullin RZ, Kashuba VI, Lerman MI, Aksenova MG, Efremov IA, Zabarovsky ER and Kiselev LL . (1997). Mol. Biol. (Mosk.), 31, 985–996.

  • Braga E, Pugacheva E, Bazov I, Ermilova V, Kazubskaya T, Mazurenko N, Kisseljov F, Liu J, Garkavtseva R, Zabarovsky E and Kisselev L . (1999). FEBS Lett., 454, 215–219.

  • Braga E, Senchenko V, Bazov I, Loginov W, Liu J, Ermilova V, Kazubskaya T, Garkavtseva R, Mazurenko N, Kisseljov F, Lerman MI, Klein G, Kisselev L and Zabarovsky ER . (2002). Int. J. Cancer, 100, 534–541.

  • Burbee DG ., Forgacs E, Zochbauer-Muller S, Shivakumar L, Fong K, Gao B, Randle D, Virmani A, Bader S, Sekido Y, Latif F, Milchgrub S, Gazdar AF, Lerman MI, Zabarovsky E, White M and Minna JD . (2001). J. Natl. Cancer Inst., 93, 691–699.

  • Cairns JP, Chiang P-W, Ramamoorthy S, Kurnit DM and Sidransky D . (1998). Clin. Cancer Res., 4, 441–444.

  • Chiang P-W, Beer DG, Wei W-L, Orringer MB and Kurnit DM . (1999). Clin. Cancer Res., 5, 1381–1386.

  • Daigo Y, Isomura M, Nishiwaki T, Tamari M, Ishikawa S, Kai M, Murata Y, Takeuchi K, Yamane Y, Hayashi R, Minami M, Fujino MA, Hojo Y, Uchiyama I, Takagi T and Nakamura Y . (1999). DNA Res., 6, 37–44.

  • Dammann R, Li C, Yoon J-H, Chin P L, Bates S and Pfeifer GP . (2000). Nat. Genet., 25, 315–319.

  • De Nooij-vanDalen AG, van Buuren-van Seggelen VHA, Lohman PHM and Giphart-Gassler M . (1998). Genes Chromosomes Cancer, 21, 30–38.

  • Dreijerink K, Braga E, Kuzmin I, Geil L, Duh F-M, Angeloni D, Zbar B, Lerman MI, Stanbridge EJ, Minna JD, Protopopov A, Li J, Kashuba V, Klein G and Zabarovsky ER . (2001). Proc. Natl. Acad. Sci. USA, 98, 7504–7509.

  • Fouret PJ, Dabit D, Mergui JL and Uzan S . (1998). Pathobiology, 66, 306–310.

  • Guo Z, Wilander E, Sallstrom J and Ponten J . (1998). Anticancer Res., 18, 707–712.

  • Guo Z, Hu X, Afink G, Ponten F, Wilander E and Ponten J . (2000). Int. J. Cancer, 86, 518–523.

  • Guo Z, Wu F, Asplund A, Hu X, Mazurenko N, Kisseljov F, Ponten J and Wilander E . (2001). Mod. Pathol., 14, 54–61.

  • Heid CA, Stevens J, Livak KJ and Williams PM . (1996). Genome Res., 6, 986–994.

  • Helland A, Kraggerud SM, Kristensen GB, Holm R, Abeler VM, Huebner K, Borresen-Dale AL and Lothe RA . (2000). Int. J. Cancer, 88, 217–222.

  • Herzog CR, Keith AC, Sabourin CLK, Kelloff GJ, Boone CW, Stoner GD and You M . (2001). Mol. Carcinog., 30, 159–168.

  • Ishikawa S, Kai M, Tamari M, Takei Y, Takeuchi K, Bandou H, Yamane Y, Ogawa M and Nakamura Y . (1997). DNA Res., 4, 35–43.

  • Kashuba VI, Gizatullin RZ, Protopopov AI, Li J, Vorobieva NV, Fedorova L, Zabarovska VI, Muravenko OV, Kost-Alimova M, Domninsky DA, Kiss C, Allikmets R, Zakharyev VM, Braga EA, Sumegi J, Lerman M, Wahlestedt C, Zelenin AV, Sheer D, Winberg G, Grafodatsky A, Kisselev LL, Klein G and Zabarovsky ER . (1999). Gene, 239, 259–271.

  • Kashuba VI, Szeles A, Allikmets RL, Nilsson AS, Bergerheim SR, Modi W, Grafodatsky A, Dean M, Stanbridge EJ, Winberg G, Klein G and Zabarovsky ER . (1995). Cancer Genet. Cytogenet., 81, 144–150.

  • Kisseljov F, Semionova L, Samoylova E, Mazurenko N, Komissarova E, Zourbitskaya V, Gritzko T, Kozachenko V, Netchushkin M, Petrov S, Smirnov A and Alonso A . (1996). Int. J. Cancer, 69, 484–487.

  • Kok K, Naylor SL and Buys CH . (1997). Adv. Cancer Res., 71, 27–92.

  • Kuzmin I, Gillespie JW, Protopopov A, Geil L, Dreijerink K, Yang Y, Vocke CD, Duh F-M, Zabarovsky E, Rhim JS, Emmert-Buck MR, Linehan WM and Lerman ML . (2002). Cancer Res., 62, 3498–3502.

  • Larson AA, Kern S, Curtiss SH, Gordon R, Cavenee W and Hampton GM . (1997a). Cancer Res., 57, 4082–4090.

  • Larson AA, Liao S-Y, Stanbridge EJ, Cavenee WK and Hampton GM . (1997b). Cancer Res., 57, 4171–4176.

  • Lazo PA . (1999). Br. J. Cancer, 80, 2008–2019.

  • Lerman M, Minna J, Sekido Y, Bader S, Burbee D, Fong K, Forgacs E, Gao B, Garner H, Gazdar AF, Girard L, Kamibayashi C, Kondo M, Pande A, Ramalingam V, Randle D, Tomizawa Y, Virmani A, Wistuba I, Macartney D, Honorio S, Maher E, Latif F, Kashuba V, Protopopov A, Li J, Klein G, Zabarovsky E, Duh F-M, Wei M-H, Geil L, Kuzmin I, Ivanov S, Angeloni D, Ivanova A, Zbar B and Johnson BE . (2000). Cancer Res., 60, 6116–6133.

  • Liu J, Zabarovska VI, Braga E, Alimov A, Klein G and Zabarovsky ER . (1999). FEBS Lett., 462, 121–128.

  • Livak KJ, Flood SJ, Marmaro J, Giusti W and Deets K . (1995). PCR Methods Appl., 4, 357–362.

  • Mantel N . (1967). Cancer Res., 27, 209–220.

  • Matthews CP, Shera KA and McDougall JK . (2000). Proc. Soc. Exp. Biol. Med., 223, 316–321.

  • Mazurenko N, Attaleb M, Gritsko T, Semjonova L, Pavlova L, Sakharova O and Kisseljov F . (1999). Oncol. Rep., 6, 859–863.

  • Muller CY, O'Boyle JD, Fong KM, Wistuba II, Biesterveld E, Ahmadian M, Miller DS, Gazdar AF and Minna JD . (1998). J. Natl. Cancer Inst., 90, 433–439.

  • Murata Y, Tamari M, Takahashi T, Horio Y, Hibi K, Yokoyama S, Inazawa J, Yamakawa A, Takahashi T and Nakamura Y . (1994). Hum. Mol. Genet., 3, 1341–1344.

  • Protopopov A, Kashuba VI, Zabarovska VI, Muravenko OV, Lerman MI, Klein G and Zabarovsky ER . (2003). Cancer Res., 63, 404–412.

  • Rader JS, Gerhard DS, O'Sullivan MJ, Li Y, Li L, Liapis H and Huettner PC . (1998). Genes Chrom. Cancer, 22, 57–65.

  • Rader JS, Kamarasova T, Huettner PC, Li L, Li Y and Gerhard DS . (1996). Oncogene, 13, 2737–2741.

  • Samoylova E, Shihaev G, Petrov S, Kisseljova N and Kisseljov F . (1995). Int. J. Cancer, 61, 337–341.

  • Sekido Y, Ahmadian M, Wistuba II, Latif F, Bader S, Wei M-H, Duh F-M, Gazdar AF, Lerman MI and Minna JD . (1998). Oncogene, 16, 3151–3157.

  • Thiagalingam S, Laken S, Willson JKV, Markowitz SD, Kinzler KW, Vogelstein B and Lengauer Ch . (2001). Proc. Natl. Acad. Sci. USA, 98, 2698–2702.

  • Umayahara K, Numa F, Suehiro Y, Sakata A, Nawata S, Ogata H, Suminami M, Sasaki K and Kato H . (2002). Genes Chromosomes Cancer, 33, 98–102.

  • Van den Berg A and Buys CH . (1997). Genes Chromosomes Cancer, 19, 59–76.

  • Varella-Garcia M, Gemmill RM, Rabenhorst SH, Lotto A, Drabkin HA, Archer PA and Franklin WA . (1998). Cancer Res., 58, 4701–4707.

  • Wei MF, Latif F, Bader S, Kashiba V, Chen JY, Duh FM, Sekido Y, Lee C, Geil L, Kuzmin I, Zabarovsky E, Klein G, Zbar B, Minna JD and Lerman MI . (1996). Cancer Res., 56, 1487–1492.

  • Wistuba II, Behrens C, Virmani AK, Meme G, Milchgrub S, Girard L, Fondon III JW, Garner HR, McKay B, Latif F, Lerman MI, Lam S, Gazdar AF and Minna JD . (2000). Cancer Res., 60, 1949–1960.

  • Wistuba II, Montellano FD, Milchgrub S, Virmani AK, Behrens C, Chen H, Ahmadian M, Nowak JA, Muller C, Minna JD and Gazdar AF . (1997). Cancer Res., 57, 3154–3158.

  • Zabarovsky ER, Lerman MI and Minna JD . (2002). Oncogene, 21, 6915–6935.

Download references

Acknowledgements

This work was supported by research grants from the Swedish Cancer Society, the Swedish Research Council, STINT, Ingabritt och Arne Lundbergs Forskningsstiftelse, Pharmacia Corporation, Karolinska Institute, the Russian National Human Genome Program and the Russian Foundation for Basic Research (Grants 01-04-48028 and 01-04-49086). MIL was funded in toto with funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-56000.

Author information

Author notes

  1. Vera Senchenko and Jian Liu: These authors contributed equally to this work

Authors and Affiliations

  1. Microbiology and Tumor Biology Center, Center for Genomics and Bioinformatics, Karolinska Institute, Stockholm, 17177, Sweden

    Vera Senchenko, Jian Liu, Eleonora Braga, Igor Bazov, Alexei Protopopov, Vladimir Kashuba, George Klein & Eugene R Zabarovsky

  2. Center ‘Bioengineering’, Russian Academy of Sciences, Moscow, 117312, Russia

    Vera Senchenko

  3. Russian State Genetics Center, Moscow, 113545, Russia

    Eleonora Braga, Witaly Loginov, Yury Seryogin & Igor Bazov

  4. Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia

    Natalia Mazurenko & Fedor L Kisseljov

  5. Cancer-Causing Genes Section, Laboratory of Immunobiology, Center for Cancer Research, National Cancer Institute, Frederick, 21702, MD, USA

    Michael I Lerman

  6. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia

    Eugene R Zabarovsky

Authors
  1. Vera Senchenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eleonora Braga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Natalia Mazurenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Witaly Loginov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yury Seryogin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Igor Bazov
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alexei Protopopov
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fedor L Kisseljov
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Vladimir Kashuba
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Michael I Lerman
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. George Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Eugene R Zabarovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eugene R Zabarovsky.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Senchenko, V., Liu, J., Braga, E. et al. Deletion mapping using quantitative real-time PCR identifies two distinct 3p21.3 regions affected in most cervical carcinomas. Oncogene 22, 2984–2992 (2003). https://doi.org/10.1038/sj.onc.1206429

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206429

Keywords

This article is cited by

Search

Advanced search

Quick links