Dataset Information

DNA copy number variations characterize benign and malignant thyroid tumors.

ABSTRACT:

Context

Fine-needle aspiration (FNA) is the best diagnostic tool for preoperative evaluation of thyroid nodules but is often inconclusive as a guide for surgical management.

Objective

Our hypothesis was that thyroid tumor subtypes may show characteristic DNA copy number variation (CNV) patterns, which may further improve the preoperative classification.

Design

Our study cohorts included benign follicular adenomas (FAs), classic papillary thyroid carcinomas (PTCs), and follicular variant PTCs (FVPTCs), the three subtypes most commonly associated with inconclusive preoperative cytopathology.

Setting

Tissue and FNA samples were obtained at an academic tertiary referral center.

Patients

Cases were identified that underwent partial or complete thyroidectomy for malignant or indeterminate thyroid lesions between 2000 and 2008 and had adequate snap-frozen tissue.

Interventions

Pairs of tumor tissue and matching normal thyroid tissue-derived DNA were compared using 550K single-nucleotide polymorphism arrays.

Main outcome measure

Statistically significant differences in CNV patterns between tumor subtypes were identified.

Results

Segmental amplifications in chromosomes (Ch) 7 and 12 were more common in FAs than in PTCs or FVPTCs. Additionally, a subset of FAs and FVPTCs showed deletions in Ch22. We identified the 5 CNV-associated genes best at discriminating between FAs and PTCs/FVPTCs, which correctly classified 90% of cases. These 5 Ch12 genes were validated by quantitative genomic PCR and gene expression array analyses on the same patient cohort. The 5-gene signature was then successfully validated against an independent test cohort of benign and malignant tumor samples. Finally, we performed a feasibility study on matched FA-derived intraoperative FNA samples and were able to correctly identify FAs harboring the Ch12 amplification signature, whereas FAs without amplification showed a normal Ch12 signature.

Conclusions

Thyroid tumor subtypes possess characteristic genomic profiles that may further our understanding of structural genetic changes in thyroid tumor subtypes and may lead to the development of new diagnostic biomarkers in FNA samples.

SUBMITTER: Liu Y

PROVIDER: S-EPMC3590464 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Publications

DNA copy number variations characterize benign and malignant thyroid tumors.

Liu Yan Y Cope Leslie L Sun Wenyue W Wang Yongchun Y Prasad Nijaguna N Sangenario Lauren L Talbot Kristen K Somervell Helina H Westra William W Bishop Justin J Califano Joseph J Zeiger Martha M Umbricht Christopher C

The Journal of clinical endocrinology and metabolism 20130123 3

<h4>Context</h4>Fine-needle aspiration (FNA) is the best diagnostic tool for preoperative evaluation of thyroid nodules but is often inconclusive as a guide for surgical management.<h4>Objective</h4>Our hypothesis was that thyroid tumor subtypes may show characteristic DNA copy number variation (CNV) patterns, which may further improve the preoperative classification.<h4>Design</h4>Our study cohorts included benign follicular adenomas (FAs), classic papillary thyroid carcinomas (PTCs), and folli ...[more]

PMID: 23345095

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Project description:BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare and highly aggressive soft tissue tumors showing complex chromosomal aberrations. In order to identify recurrent chromosomal regions of gain and loss, and thereby novel gene targets of potential importance for MPNST development and/or progression, we have analyzed DNA copy number changes in seven high-grade MPNSTs using microarray-based comparative genomic hybridization (array CGH). RESULTS: Considerable more gains than losses were observed, and the most frequent minimal recurrent regions of gain included 1q24.1-q24.2, 1q24.3-q25.1, 8p23.1-p12, 9q34.11-q34.13 and 17q23.2-q25.3, all gained in five of seven samples. The 17q23.2-q25.3 region was gained in all five patients with poor outcome and not in the two patients with disease-free survival. cDNA microarray analysis and quantitative real-time reverse transcription PCR were used to investigate expression of genes located within these regions. The gene lysyl oxidase-like 2 (LOXL2) was identified as a candidate target for the 8p23.1-p12 gain. Within 17q, the genes topoisomerase II-alpha (TOP2A), ets variant gene 4 (E1A enhancer binding protein, E1AF) (ETV4) and baculoviral IAP repeat-containing 5 (survivin) (BIRC5) showed increased expression in all samples compared to two benign tumors. Increased expression of these genes has previously been associated with poor survival in other malignancies, and for TOP2A, in MPNSTs as well. In addition, we have analyzed the expression of five micro RNAs located within the 17q23.2-q25.3 region, but none of them showed high expression levels compared to the benign tumors. CONCLUSION: Our study shows the potential of using DNA copy number changes obtained by array CGH to predict the prognosis of MPNST patients. Although no clear correlations between the expression level and patient outcome were observed, the genes TOP2A, ETV4 and BIRC5 are interesting candidate targets for the 17q gain associated with poor survival.

Dataset Information

DNA copy number variations characterize benign and malignant thyroid tumors.

Context

Objective

Design

Setting

Patients

Interventions

Main outcome measure

Results

Conclusions

Publications

DNA copy number variations characterize benign and malignant thyroid tumors.

Similar Datasets

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