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Genetic imbalances detected by multiplex ligation-dependent probe amplification in a cohort of patients with oral squamous cell carcinoma—the first step towards clinical personalized medicine

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Tumor Biology

Abstract

Oral tumors are a growing health problem worldwide; thus, it is mandatory to establish genetic markers in order to improve diagnosis and early detection of tumors, control relapses and, ultimately, delineate individualized therapies. This study was the first to evaluate and discuss the clinical applicability of a multiplex ligation-dependent probe amplification (MLPA) probe panel directed to head and neck cancer. Thirty primary oral squamous cell tumors were analyzed using the P428 MLPA probe panel. We detected genetic imbalances in 26 patients and observed a consistent pattern of distribution of genetic alterations in terms of losses and gains for some chromosomes, particularly for chromosomes 3, 8, and 11. Regarding the latter, some specific genes were highlighted due to frequent losses of genetic material—RARB, FHIT, CSMD1, GATA4, and MTUS1—and others due to gains—MCCC1, MYC, WISP1, PTK2, CCND1, FGF4, FADD, and CTTN. We also verified that the gains of MYC and WISP1 genes seem to suggest higher propensity of tumors localized in the floor of the mouth. This study proved the value of this MLPA probe panel for a first-tier analysis of oral tumors. The probemix was developed to include target regions that have been already shown to be of diagnostic/prognostic relevance for oral tumors. Furthermore, this study emphasized several of those specific genetic targets, suggesting its importance to oral tumor development, to predict patients’ outcomes, and also to guide the development of novel molecular therapies.

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Acknowledgments

The authors are grateful to Dr. Artur Ferreira, Director of Maxillofacial Surgery Unit from Coimbra Hospital and University Centre, for the contribution in the collection of the samples. This work was supported in part by CIMAGO (Center of Investigation on Environment Genetics and Oncobiology, Faculty of Medicine, University of Coimbra).

Conflicts of interest

W. Rifi and S. Savola are employed by MRC-Holland, manufacturer of commercially available MLPA probemixes. All other authors declare no competing financial interests.

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Authors and Affiliations

  1. Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal

    Ilda Patrícia Ribeiro, José Ferrão, Joana Barbosa de Melo & Isabel Marques Carreira

  2. Center of Investigation on Environment Genetics and Oncobiology (CIMAGO). Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal

    Ilda Patrícia Ribeiro, Francisco Marques, Joana Barbosa de Melo, Isabel Poiares Baptista & Isabel Marques Carreira

  3. Department of Dentistry, Faculty of Medicine, University of Coimbra, 3000-075, Coimbra, Portugal

    Francisco Marques & Isabel Poiares Baptista

  4. Stomatology Unit, Coimbra Hospital and University Centre, CHUC, EPE, 3000-075, Coimbra, Portugal

    Francisco Marques

  5. Laboratory of Biostatistics and Medical Informatics, IBILI—Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal

    Francisco Caramelo

  6. Molecular Pathology Laboratory, Portuguese Institute of Oncology of Coimbra FG, EPE, 3000-075, Coimbra, Portugal

    Hugo Prazeres

  7. Department of Pathology, Coimbra Hospital and University Centre, CHUC, EPE, 3000-075, Coimbra, Portugal

    Maria José Julião

  8. Department of Tumor Diagnostics, MRC-Holland, 1057DN, Amsterdam, Finland

    Widad Rifi & Suvi Savola

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  1. Ilda Patrícia Ribeiro
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  2. Francisco Marques
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  4. José Ferrão
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  8. Suvi Savola
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  9. Joana Barbosa de Melo
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  10. Isabel Poiares Baptista
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  11. Isabel Marques Carreira
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Correspondence to Isabel Marques Carreira.

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Ribeiro, I.P., Marques, F., Caramelo, F. et al. Genetic imbalances detected by multiplex ligation-dependent probe amplification in a cohort of patients with oral squamous cell carcinoma—the first step towards clinical personalized medicine. Tumor Biol. 35, 4687–4695 (2014). https://doi.org/10.1007/s13277-014-1614-9

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  • DOI: https://doi.org/10.1007/s13277-014-1614-9

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