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Insertion/deletion polymorphisms are convenient and reliable markers to assess chromosomal instability in human tumors

Insertion/deletion polymorphisms are convenient and reliable markers to assess chromosomal instability in human tumors

Int J Biol Markers 2012; 27(3): 232 - 240

Article Type: ORIGINAL ARTICLE

DOI:10.5301/JBM.2012.9308

Authors

Agnès Marchio, Abdellah Akil, Benoît Terris, Anne Dejean, Pascal Pineau

Abstract

Chromosomal instability (CIN) is frequently associated with a poor outcome in human carcinomas. The genomes of the main human malignancies are well defined as hundreds of tumors have been characterized by arrays. Targeting the appropriate chromosomes with set of markers appears as a realistic approach for CIN assessment. We decided to test the reliability of different insertion/deletion (InDel) polymorphisms to detect allelic loss in a subset of previously characterized hepatocellular carcinomas (HCC). To this aim 3 kinds of markers, L1 insertion (n=1), Alu insertions (n=4) and Marshfield InDel (MID, n=8) markers, were tested on a series of 68 paired HCC/non-tumor liver samples that were previously characterized for loss of heterozygosity (LOH). All markers were analyzed on agarose gels and some were tested with the high resolution melting (HRM) technique. Heterozygosity of the tested markers was high with a mean of 0.489 and a range of 0.265-0.525. Using 6 markers for chromosome 8p, the sensitivity of the method was high. LOH was detected in all samples known to be affected (n=34) whereas retention was found in 29/30 samples (specificity of 96.6%). Finally, the HRM analysis applied to 2 MID markers provided consistent profiles enabling closed-tube determination of chromosomes 17p and 18q status. Overall, our work suggests that different types of InDel markers are suitable for CIN detection in human tumors and may provide convenient and useful information for basic or translational research as well as for future applications in clinical practice.

Article History

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Authors

  • Marchio, Agnès [PubMed] [Google Scholar]
    Unité “Organisation Nucléaire et Oncogenèse”, INSERM U993, Institut Pasteur, Paris - France
  • Akil, Abdellah [PubMed] [Google Scholar]
    Laboratoires des Hépatites Virales, Institut Pasteur du Maroc, Casablanca - Morocco
  • Terris, Benoît [PubMed] [Google Scholar]
    Laboratoire d’Anatomie Pathologique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris - France
  • Dejean, Anne [PubMed] [Google Scholar]
    Unité “Organisation Nucléaire et Oncogenèse”, INSERM U993, Institut Pasteur, Paris - France
  • Pineau, Pascal [PubMed] [Google Scholar]
    Unité “Organisation Nucléaire et Oncogenèse”, INSERM U993, Institut Pasteur, Paris - France

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