Skip to main content

15.03.2016 | Endocrine Tumors | Ausgabe 7/2016

Annals of Surgical Oncology 7/2016

Epigenetic Alterations and Canonical Pathway Disruption in Papillary Thyroid Cancer: A Genome-wide Methylation Analysis

Annals of Surgical Oncology > Ausgabe 7/2016
MD Michael G. White, MD Sapna Nagar, PhD Briseis Aschebrook-Kilfoy, MD, PhD Farzana Jasmine, MD, PhD Muhammad G. Kibriya, MD, MMedSC Habibul Ahsan, MD, PhD Peter Angelos, MD Edwin L. Kaplan, MD Raymon H. Grogan
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1245/​s10434-016-5185-4) contains supplementary material, which is available to authorized users.



Alterations in DNA methylation have been demonstrated in a variety of malignancies, including papillary thyroid cancer (PTC). The full extent of dysregulation in PTC and the downstream affected pathways remains unclear. Here we report a genome-wide analysis of PTC methylation, the dysregulation of various canonical pathways, and assess its potential as a diagnostic test.


A discovery set utilized 49 PTCs and matched normal controls from The Cancer Genome Atlas. Another set of 16 PTCs and 13 normal controls were used as a replication set. Genome-wide methylation analysis was done using Illumina 450 K methylation chips. Differentially methylated loci (DML) were identified by comparing PTC and matched normal tissues. DML were defined as false-discovery rate p < 0.05 and absolute Δβ ≥ 0.2. DML were then analyzed for pathway and disease commonalities using Qiagen Ingenuity Pathway Analysis.


Of 485,577 CpG sites analyzed, 1226 DML were identified in our discovery and replication sets, and 1061 (86.5 %) DML showed hypomethylation when comparing tumor with normal tissue. Support vector machine classification was able to differentiate benign from malignant tissue in 107 (94.7 %) of 113 tested samples, including 15 (83.3 %) of 18 samples lacking a clearly deleterious mutation. Statistically significant associations with multiple canonical pathways, diseases, and biofunctions were observed including PI3K, PTEN, wnt/β-catenin, and p53.


Epigenetic dysregulation of multiple canonical pathways are associated with the development of PTC. This methylation signature shows promise as a future adjunctive screening test for thyroid nodules.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

Weitere Produktempfehlungen anzeigen
Supplementary material 1 (DOCX 482 kb)
Supplementary material 2 (DOCX 490 kb)
Supplementary material 3 (DOCX 528 kb)
Über diesen Artikel

Weitere Artikel der Ausgabe 7/2016

Annals of Surgical Oncology 7/2016 Zur Ausgabe
  1. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.

  2. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.

Neu im Fachgebiet Chirurgie

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Chirurgie und bleiben Sie gut informiert – ganz bequem per eMail.