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Clinical Research (Excluding Clinical Trials)

Abstract 4268: DNA copy number variation and driver mutation patterns of follicular thyroid tumors

Hyun-seok Kim, Kathleen Wilsbach, Aurelien Marti, Alireza Najafian, Alan K. Meeker, James R. Eshleman, Justin A. Bishop, Martha Zeiger and Christopher B. Umbricht
Hyun-seok Kim
Johns Hopkins Hospital, Baltimore, MD.
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Kathleen Wilsbach
Johns Hopkins Hospital, Baltimore, MD.
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Aurelien Marti
Johns Hopkins Hospital, Baltimore, MD.
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Alireza Najafian
Johns Hopkins Hospital, Baltimore, MD.
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Alan K. Meeker
Johns Hopkins Hospital, Baltimore, MD.
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James R. Eshleman
Johns Hopkins Hospital, Baltimore, MD.
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Justin A. Bishop
Johns Hopkins Hospital, Baltimore, MD.
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Martha Zeiger
Johns Hopkins Hospital, Baltimore, MD.
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Christopher B. Umbricht
Johns Hopkins Hospital, Baltimore, MD.
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DOI: 10.1158/1538-7445.AM2015-4268 Published August 2015
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Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA

Abstract

Background

Our previous study using single nucleotide polymorphism (SNP) array identified significant differences in copy number variation (CNV) between tumor subtypes. This study was conducted to extend our previous findings, using both Fluorescent In-Situ Hybridization (FISH) and quantitative PCR (qPCR), and to investigate the possible relationship with major thyroid cancer driver mutations, and their association with aggressive features in follicular thyroid tumors.

Methods

For the validation, we obtained paraffin blocks of all cases with CNVs identified in our prior study (7 samples with Ch12 amplification, and 6 samples with Ch22 deletion), as well as 6 control samples with no CNV, for FISH analysis and qPCR. We used centromeric and distal probes to differentiate partial vs whole chromosome alterations. We then extended the study to characterize the relation between CNV and driver mutations and possible associations with aggressive features in a larger cohort of tumors, consisting of: 35 follicular adenoma (FA), 19 non-aggressive follicular variant papillary thyroid carcinoma (FVPTC), 22 aggressive FVPTC, 16 non-aggressive follicular carcinoma (FC), and 15 aggressive FC.

Results

Our FISH and qPCR results confirmed our earlier CNV results in this expanded sample cohort. Furthermore, FISH indicated that in each case, CNV involved the entire chromosome rather than sub-chromosomal alterations. Ch12 amplification was significantly more prevalent in FA and non-aggressive tumor than aggressive tumor subtypes (p-value <0.01). The HRAS mutation was predominantly detected in aggressive FCs, but the low number of events precluded reaching statistical significance.

Conclusion

Our study suggests that Ch12 amplification is associated with indolent tumors. Since FAs are a common source of inconclusive pre-operative cytopathology, a molecular signature such as Ch12 amplification that identifies follicular tumors with little aggressive potential could be useful. Further independent external testing is warranted.

CNV and RAS pattern across follicular thyroid tumor subtypes
Chromosome 12 AmplificationChromosome 22 DeletionNRAS mutationHRAS mutation
FA40% (14/35)17.1% (6/35)17.1% (6/35)0.3% (1/35)
Non-aggressive FVPTC15.8% (3/19)15.8% (3/19)36.8% (7/19)0% (0/19)
Aggressive FVPTC4.5% (1/22)22.7% (5/22)18.2% (4/22)0% (0/22)
Non-aggressive FC6.3% (1/16)6.3% (1/16)50% (8/16)0% (0/16)
Aggressive FC6.7% (1/15)26.7% (4/15)53.3% (8/15)26.7% (4/15)

Citation Format: Hyun-seok Kim, Kathleen Wilsbach, Aurelien Marti, Alireza Najafian, Alan K. Meeker, James R. Eshleman, Justin A. Bishop, Martha Zeiger, Christopher B. Umbricht. DNA copy number variation and driver mutation patterns of follicular thyroid tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4268. doi:10.1158/1538-7445.AM2015-4268

  • ©2015 American Association for Cancer Research.
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Cancer Research: 75 (15 Supplement)
August 2015
Volume 75, Issue 15 Supplement
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Abstract 4268: DNA copy number variation and driver mutation patterns of follicular thyroid tumors
Hyun-seok Kim, Kathleen Wilsbach, Aurelien Marti, Alireza Najafian, Alan K. Meeker, James R. Eshleman, Justin A. Bishop, Martha Zeiger and Christopher B. Umbricht
Cancer Res August 1 2015 (75) (15 Supplement) 4268; DOI: 10.1158/1538-7445.AM2015-4268

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Abstract 4268: DNA copy number variation and driver mutation patterns of follicular thyroid tumors
Hyun-seok Kim, Kathleen Wilsbach, Aurelien Marti, Alireza Najafian, Alan K. Meeker, James R. Eshleman, Justin A. Bishop, Martha Zeiger and Christopher B. Umbricht
Cancer Res August 1 2015 (75) (15 Supplement) 4268; DOI: 10.1158/1538-7445.AM2015-4268
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Cancer Research Online ISSN: 1538-7445
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