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Concurrent analysis of loss of heterozygosity (LOH) and copy number abnormality (CNA) for oral premalignancy progression using the Affymetrix 10K SNP mapping array

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Abstract

Like most human cancers, oral squamous cell carcinoma (SCC) is characterized by genetic instabilities. In this study, a single platform (Affymetrix 10K SNP mapping array) was used to generate both loss of heterozygosity (LOH) and DNA copy number abnormality (CNA) read-outs for precise and high-resolution genetic alteration profiles. As a proof of principle, we performed this concordant analysis on a panel of deletion and trisomy cell lines with known chromosomal alterations and the precise LOH and CNA regions were detected as expected. Using a previously described oral SCC progression model system, we identified a set of genomic regions that may be associated with the malignancy progression, including chromosome regions 3pter–3p35.3, 3p14.1–3p13, 11p, 11q14.3–11q22.2, and 11q13.5–11q14.1. These data show that it is feasible to utilize high-density SNP arrays to generate concordant LOH and CNA profiles at high resolution.

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References

  • Alimov A, Kost-Alimova M, Liu J, Li C, Bergerheim U, Imreh S, Klein G, Zabarovsky ER (2000) Combined LOH/CGH analysis proves the existence of interstitial 3p deletions in renal cell carcinoma. Oncogene 19:1392–1399

    Article  CAS  Google Scholar 

  • Bignell GR, Huang J, Greshock J, Watt S, Butler A, West S, Grigorova M, Jones KW, Wei W, Stratton MR, Futreal PA, Weber B, Shapero MH, Wooster R (2004) High-resolution analysis of DNA copy number using oligonucleotide microarrays. Genome Res 14:287–295

    Article  CAS  Google Scholar 

  • Ding H, Han C, Gibson-D’Ambrosio R, Steele VE, D’Ambrosio SM (2003) Piroxicam selectively inhibits the growth of premalignant and malignant human oral cell lines by limiting their progression through the S phase and reducing the levels of cyclins and AP-1. Int J Cancer 107:830–836

    Article  CAS  Google Scholar 

  • Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396:643–649

    Article  CAS  Google Scholar 

  • Li C, Wong WH (2001a) Model-based analysis of oligonucleotide arrays: model validation, design issues and standard error application. Genome Biol 2(8):Research0032.1–0032.11

    Google Scholar 

  • Li C, Wong WH (2001b) Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. Proc Natl Acad Sci USA 98:31–36

    Article  CAS  Google Scholar 

  • Li C, Wong WH (2003) DNA-Chip Analyzer (dChip). In: Parmigiani G, Garrett ES, Irizarry RA, Zeger SL (eds) The analysis of gene expression data: methods and software. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Lin M, Wei LJ, Sellers WR, Lieberfarb M, Wong WH, Li C (2004). dChipSNP: significance curve and clustering of SNP-array-based loss-of-heterozygosity data. Bioinformatics 20:1233–1240

    Article  CAS  Google Scholar 

  • Milo GE, Shuler C, Kurian P, French BT, Mannix DG, Noyes I, Hollering J, Sital N, Schuller D, Trewyn RW (1990) Nontumorigenic squamous cell carcinoma line converted to tumorigenicity with methyl methanesulfonate without activation of HRAS or MYC. Proc Natl Acad Sci USA 87:1268–1272

    CAS  Google Scholar 

  • Park NH, Min BM, Li SL, Huang MZ, Cherick HM, Doniger J (1991) Immortalization of normal human oral keratinocytes with type 16 human papillomavirus. Carcinogenesis 12:1627–1631

    CAS  Google Scholar 

  • Popescu NC, Zimonjic DB (1997) Molecular cytogenetic characterization of cancer cell alterations. Cancer Genet Cytogenet 93:10–21

    Article  CAS  Google Scholar 

  • Zhou X, Cole SW, Hu S, Wong DTW (2004a) Detection of DNA copy number abnormality by microarray expression analysis. Hum Genet 114:464–467

    Article  CAS  Google Scholar 

  • Zhou X, Li C, Mok SC, Chen Z, Wong DTW (2004b) Whole genome loss of heterozygosity profiling on oral squamous cell carcinoma by high-density single nucleotide polymorphic allele (SNP) array. Cancer Genet Cytogenet 151:82–84

    CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by NIH PHS grants R21 CA94216 and R01 DE015970-01 (to D.W.), R33 CA103595 (to S.M.), T32 DE07296-07 and a CRPFA fellowship (to X.Z.). The 10K SNP mapping array hybridization and scanning were done in the UCLA DNA microarray facility. The primary NHOK cell was a gift from Dr. N.H. Park and K.H. Shin of the UCLA School of Dentistry. The 830182SCC and 830182CA cell lines were gifts from Dr. G. Milo and S. D’Ambrosio of the Ohio State University.

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Authors and Affiliations

  1. School of Dentistry, Dental Research Institute, University of California at Los Angeles, P.O. Box 951668, Los Angeles, CA 90095-1668, USA

    Xiaofeng Zhou, Yang Li & David T. W. Wong

  2. Laboratory of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Samuel C. Mok

  3. Department of Human Genetics, School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    Zugen Chen

  4. Division of Oral Biology and Medicine, School of Dentistry, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA

    David T. W. Wong

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  1. Xiaofeng Zhou
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  2. Samuel C. Mok
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  3. Zugen Chen
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  4. Yang Li
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  5. David T. W. Wong
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Correspondence to David T. W. Wong.

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Zhou, X., Mok, S.C., Chen, Z. et al. Concurrent analysis of loss of heterozygosity (LOH) and copy number abnormality (CNA) for oral premalignancy progression using the Affymetrix 10K SNP mapping array. Hum Genet 115, 327–330 (2004). https://doi.org/10.1007/s00439-004-1163-1

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  • DOI: https://doi.org/10.1007/s00439-004-1163-1

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