TY - JOUR

T1 - Molecular signatures of thyroid follicular neoplasia

AU - Helweg-Larsen, Rehannah Borup

AU - Rossing, Maria

AU - Henao Giraldo, Ricardo

AU - Yamamoto, Yohei

AU - Krogdahl, Annelise

AU - Godballe, Christian

AU - Winther, Ole

AU - Kiss, Katalin

AU - Christensen, Lise Hanne

AU - Høgdall, Estrid Vilma Solyom

AU - Bennedbæk, Finn Noe

AU - Nielsen, Finn Cilius

PY - 2010

Y1 - 2010

N2 - The molecular pathways leading to thyroid follicular neoplasia are incompletely understood, and the diagnosis of follicular tumors is a clinical challenge. To provide leads to the pathogenesis and diagnosis of the tumors, we examined the global transcriptome signatures of follicular thyroid carcinoma (FC) and normofollicular adenoma (FA) as well as fetal/microFA (fetal adenoma). Carcinomas were strongly enriched in transcripts encoding proteins involved in DNA replication and mitosis corresponding to increased number of proliferating cells and depleted number of transcripts encoding factors involved in growth arrest and apoptosis. In the latter group, the combined loss of transcripts encoding the nuclear orphan receptors NR4A1 and NR4A3, which were recently shown to play a causal role in hematopoetic neoplasia, was noteworthy. The analysis of differentially expressed transcripts provided a mechanism for cancer progression, which is why we exploited the results in order to generate a molecular classifier that could identify 95% of all carcinomas. Validation employing public domain and cross-platform data demonstrated that the signature was robust and could diagnose follicular nodules originating from different geographical locations and platforms with similar accuracy. We came to the conclusion that down-regulation of factors involved in growth arrest and apoptosis may represent a decisive step in the pathogenesis of FC. Moreover, the described molecular pathways provide an accurate and robust genetic signature for the diagnosis of FA and FC.

AB - The molecular pathways leading to thyroid follicular neoplasia are incompletely understood, and the diagnosis of follicular tumors is a clinical challenge. To provide leads to the pathogenesis and diagnosis of the tumors, we examined the global transcriptome signatures of follicular thyroid carcinoma (FC) and normofollicular adenoma (FA) as well as fetal/microFA (fetal adenoma). Carcinomas were strongly enriched in transcripts encoding proteins involved in DNA replication and mitosis corresponding to increased number of proliferating cells and depleted number of transcripts encoding factors involved in growth arrest and apoptosis. In the latter group, the combined loss of transcripts encoding the nuclear orphan receptors NR4A1 and NR4A3, which were recently shown to play a causal role in hematopoetic neoplasia, was noteworthy. The analysis of differentially expressed transcripts provided a mechanism for cancer progression, which is why we exploited the results in order to generate a molecular classifier that could identify 95% of all carcinomas. Validation employing public domain and cross-platform data demonstrated that the signature was robust and could diagnose follicular nodules originating from different geographical locations and platforms with similar accuracy. We came to the conclusion that down-regulation of factors involved in growth arrest and apoptosis may represent a decisive step in the pathogenesis of FC. Moreover, the described molecular pathways provide an accurate and robust genetic signature for the diagnosis of FA and FC.

U2 - 10.1677/ERC-09-0288

DO - 10.1677/ERC-09-0288

M3 - Journal article

C2 - 20668010

VL - 17

SP - 691

EP - 708

JO - Endocrine - Related Cancer

JF - Endocrine - Related Cancer

SN - 1351-0088

IS - 3

ER -