Open Access

Whole‑exome sequencing identifies variants in invasive pituitary adenomas

  • Authors:
    • Xiaolei Lan
    • Hua Gao
    • Fei Wang
    • Jie Feng
    • Jiwei Bai
    • Peng Zhao
    • Lei Cao
    • Songbai Gui
    • Lei Gong
    • Yazhuo Zhang
  • View Affiliations

  • Published online on: August 16, 2016     https://doi.org/10.3892/ol.2016.5029
  • Pages: 2319-2328
  • Copyright: © Lan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pituitary adenomas exhibit a wide range of behaviors. The prediction of invasion or malignant behavior in pituitary adenomas remains challenging. The objective of the present study was to identify the genetic abnormalities associated with invasion in sporadic pituitary adenomas. In the present study, the exomes of six invasive pituitary adenomas (IPA) and six non‑invasive pituitary adenomas (nIPA) were sequenced by whole‑exome sequencing. Variants were confirmed by dideoxynucleotide sequencing, and candidate driver genes were assessed in an additional 28 pituitary adenomas. A total of 15 identified variants were mainly associated with angiogenesis, metabolism, cell cycle phase, cellular component organization, cytoskeleton and biogenesis immune at a cellular level, including 13 variants that occurred as single nucleotide variants and 2 that comprised of insertions. The messenger RNA (mRNA) levels of diffuse panbronchiolitis critical region 1 (DPCR1), KIAA0226, myxovirus (influenza virus) resistance, proline‑rich protein BstNI subfamily 3, PR domain containing 2, with ZNF domain, RIZ1 (PRDM2), PR domain containing 8 (PRDM8), SPANX family member N2 (SPANXN2), TRIO and F‑actin binding protein and zinc finger protein 717 in IPA specimens were 50% decreased compared with nIPA specimens. In particular, DPCR1, PRDM2, PRDM8 and SPANXN2 mRNA levels in IPA specimens were approximately four‑fold lower compared with nIPA specimens (P=0.003, 0.007, 0.009 and 0.004, respectively). By contrast, the mRNA levels of dentin sialophospho protein, EGF like domain, multiple 7 (EGFL7), low density lipoprotein receptor‑related protein 1B and dynein, axonemal, assembly factor 1 (LRRC50) were increased in IPA compared with nIPA specimens (P=0.041, 0.037, 0.022 and 0.013, respectively). Furthermore, decreased PRDM2 expression was associated with tumor recurrence. The findings of the present study indicate that DPCR1, EGFL7, the PRDM family and LRRC50 in pituitary adenomas are modifiers of tumorigenesis, and most likely contribute to the development of oncocytic change and to the invasive tumor phenotype.
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October-2016
Volume 12 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Lan X, Gao H, Wang F, Feng J, Bai J, Zhao P, Cao L, Gui S, Gong L, Zhang Y, Zhang Y, et al: Whole‑exome sequencing identifies variants in invasive pituitary adenomas. Oncol Lett 12: 2319-2328, 2016.
APA
Lan, X., Gao, H., Wang, F., Feng, J., Bai, J., Zhao, P. ... Zhang, Y. (2016). Whole‑exome sequencing identifies variants in invasive pituitary adenomas. Oncology Letters, 12, 2319-2328. https://doi.org/10.3892/ol.2016.5029
MLA
Lan, X., Gao, H., Wang, F., Feng, J., Bai, J., Zhao, P., Cao, L., Gui, S., Gong, L., Zhang, Y."Whole‑exome sequencing identifies variants in invasive pituitary adenomas". Oncology Letters 12.4 (2016): 2319-2328.
Chicago
Lan, X., Gao, H., Wang, F., Feng, J., Bai, J., Zhao, P., Cao, L., Gui, S., Gong, L., Zhang, Y."Whole‑exome sequencing identifies variants in invasive pituitary adenomas". Oncology Letters 12, no. 4 (2016): 2319-2328. https://doi.org/10.3892/ol.2016.5029