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Discovery of frequent homozygous deletions in chromosome 3p21.3 LUCA and AP20 regions in renal, lung and breast carcinomas

Oncogene volume 23, pages 5719–5728 (2004)Cite this article

Abstract

We searched for chromosome 3p homo- and hemizygous losses in 23 lung cancer cell lines, 53 renal cell and 22 breast carcinoma biopsies using 31 microsatellite markers located in frequently deleted 3p regions. In addition, two sequence-tagged site markers (NLJ-003 and NL3-001) located in the Alu-PCR clone 20 region (AP20) and lung cancer (LUCA) regions, respectively, were used for quantitative real-time PCR (QPCR). We found frequent (10–18%) homozygous deletions (HDs) in both 3p21.3 regions in the biopsies and lung cancer cell lines. In addition, we discovered that amplification of 3p is a very common (15–42.5%) event in these cancers and probably in other epithelial malignancies. QPCR showed that aberrations of either NLJ-003 or NL3-001 were detected in more than 90% of all studied cases. HDs were frequently detected simultaneously both in NLJ-003 or NL3-001 loci in the same tumour (P<3–10−7). This observation suggests that tumour suppressor genes (TSG) in these regions could have a synergistic effect. The exceptionally high frequency of chromosome aberrations in NLJ-003 and NL3-001 loci suggests that multiple TSG(s) involved in different malignancies are located very near to these markers. Precise mapping of 15 independent HDs in the LUCA region allowed us to establish the smallest HD region in 3p21.3C located between D3S1568 (CACNA2D2 gene) and D3S4604 (SEMA3F gene). This region contains 17 genes. Mapping of 19 HDs in the AP20 region resulted in the localization of the minimal region to the interval flanked by D3S1298 and D3S3623 markers. Only four genes were discovered in this interval, namely, APRG1, ITGA9, HYA22 and VILL.

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Abbreviations

ACTB :

human β-actin gene

AI:

allelic imbalance

AP20:

Alu-PCR clone 20 region

BC:

breast carcinoma

C:

centromeric

CC:

cervical carcinoma

H-allele:

high-molecular-weight allele

HD:

homozygous deletion

L-allele:

low-molecular-weight allele

LOH:

loss of heterozygosity

LUCA:

lung cancer region

MEC:

major epithelial carcinomas

NSCLC:

non-small cell lung cancer

PF2K :

phosph-fructo-2 kinase gene

QPCR:

quantitative real-time PCR

RCC:

renal cell carcinoma

STS:

sequence-tagged site

SCLC:

small-cell lung cancer

T:

telomeric

TSG:

tumour suppressor gene

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Acknowledgements

This work was supported by research grants from the Swedish Cancer Society, the Swedish Research Council, the Swedish Foundation for International Cooperation in Research and Higher Education (STINT), Karolinska Institute, Åke Wibergs Stiftelse, the Royal Swedish Academy of Sciences, the Swedish Institute, INTAS, the Russian Foundation for Basic Research (Grant 01-04-48028), the research programme of Russian Academy of Science ‘Basic Science to Medicine’ and Russian Ministry of Science and Technology. MIL and DA were funded in toto with funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-56000. JDM was supported by Grants P50CA70907 and CA71618. The content of the publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government.

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Authors and Affiliations

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

    Vera N Senchenko, Jian Liu, Igor Bazov, Veronika I Zabarovska, Vladimir I Kashuba, George Klein, Eleonora A Braga & Eugene R Zabarovsky

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

    Vera N Senchenko

  3. Russian State Genetics Center, Moscow, 117545, Russia

    Witaly Loginov, Igor Bazov, Yury Seryogin & Eleonora A Braga

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

    Debora Angeloni & Michael I Lerman

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

    Valeria Ermilova, Tatiana Kazubskaya & Raisa Garkavtseva

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

    Lev L Kisselev & Eugene R Zabarovsky

  7. Hamon Center for Therapeutic Oncology, Research, University of Texas Southwestern Medical Center, Dallas, 75390, TX, USA

    John D Minna

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  1. Vera N Senchenko
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  10. Veronika I Zabarovska
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Correspondence to Eugene R Zabarovsky.

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Senchenko, V., Liu, J., Loginov, W. et al. Discovery of frequent homozygous deletions in chromosome 3p21.3 LUCA and AP20 regions in renal, lung and breast carcinomas. Oncogene 23, 5719–5728 (2004). https://doi.org/10.1038/sj.onc.1207760

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