Skip to main content

Frequent microdeletions in conventional papillary thyroid carcinoma detected by high-density oligonucleotide microarrays

Background

The valine to glutamate substitution at codon 600 in exon 15 of the BRAF gene (V600E) is the major driver mutation in papillary thyroid carcinomas (PTCs). Contribution of genomic gains and losses to onset and progression of PTC is far less known. We assessed genomic imbalances in PTCs by utilizing high-density oligonucleotide arrays.

Materials and methods

We used SurePrint G3 human CGH+SNP, 2×400K, microarrays to assess gains and losses in 47 PTCs in comparison to male and female human reference DNA. Interpretation of results was accomplished by using the HG19 version of the design file and the default analysis method of the Cytogenomics 2.7 research software [1]. To compare BRAF mutant (BRAFmut) PTCs with BRAF wild type (BRAFwt) PTCs, the BRAF mutational status was established in 42 cases by direct sequencing the mutational hotspot region in exon 15 [2].

Results

Whole chromosome/chromosome arm imbalances (e.g., -1p, -16q, -19) were only infrequently observed and one case was in the triploid stage. The predominant forms of imbalances were microdeletions that were in general more pronounced in both BRAFmut PTCs (N=27) and BRAFwt PTCs (N=15). These microdeletions, observed in 40% or more of the cases, include known and yet unknown thyroid cancer susceptibility genes, for example TAF12 & RCC1 (1p, 28.8~28.9 Mb) YY1AP1 (1q, 155.7 Mb), PRKCI (2q, 169.9 Mb), GSTM2P1 & RPF2 & GTF3C6 & CDK19 (8q, 110.9~111.1 Mb), RASSF3 & TBK1 (12q, 64,5~65.2 Mb), MDM2 & NUP107 & RAP1B (12q, ~69.0~69.2 Mb), BRCA1 & NAGLU (17q, 40.6~41.1 Mb), and CDH2 (18q, ~25.5 Mb). Microamplifications, observed in 30% or more of the cases, include genes as USH2A (1q, 216.5 Mb), CTNNA2 (2p, 79.9 Mb), CLSTN2 (2q, 139.9 Mb), MSR1 (8p, 16.0 Mb), and CASP12 (11q, 104.6 Mb). Number and extent of regions with SNP homozygosity varied widely between the cases.

Conclusions

This is one of the first studies using high-density oligonucleotide arrays to survey chromosomal imbalances in conventional BRAFmut and BRAFwt PTCs enabling to detect microdeletions/microamplifications (usually < 1 Mb) affecting known or yet unknown genes related to thyroid cancer. Further studies have to reveal how the affected genes contribute to onset and/or progression of PTC besides the known implication of the BRAF gain-of-function mutation in this disease.

This study was supported by King Abdulaziz City for Science and Technology (KACST) grants 09-BIO707-03 and 09-BIO820-03.

References

  1. 1.

    [http://www.chem.agilent.com/Library/usermanuals/Public/G1662-90031_CytoGenomics_ProductOverview.pdf]

  2. 2.

    Schulten HJ, Salama S, Al-Mansouri Z, Alotibi R, Al-Ghamdi K, Al-Hamour OA, Sayadi H, Al-Aradati H, Al-Johari A, Huwait E, et al: BRAF mutations in thyroid tumors from an ethnically diverse group. Hereditary cancer in clinical practice. 2012, 10: 10-

    PubMed Central  CAS  Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Hans-Juergen Schulten.

Rights and permissions

Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Cite this article

Al-Ahmadi, A., Alotibi, R., Al-Quaiti, M. et al. Frequent microdeletions in conventional papillary thyroid carcinoma detected by high-density oligonucleotide microarrays. BMC Genomics 15, P62 (2014). https://doi.org/10.1186/1471-2164-15-S2-P62

Download citation

Keywords

  • Thyroid Cancer
  • Papillary Thyroid Carcinoma
  • BRAF Mutant
  • BRAF Gene
  • Genomic Imbalance