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Clinical Research

Abstract 1191: Somatic mutation profiling of the follicular variant of papillary thyroid cancer.

Dora Dias-Santagata, David G. McFadden, Lindsay A. Bernardo, Kerry D. Lynch, A. John Iafrate, Peter M. Sadow and Gilbert H. Daniels
Dora Dias-Santagata
Massachusetts General Hospital, Boston, MA.
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David G. McFadden
Massachusetts General Hospital, Boston, MA.
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Lindsay A. Bernardo
Massachusetts General Hospital, Boston, MA.
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Kerry D. Lynch
Massachusetts General Hospital, Boston, MA.
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A. John Iafrate
Massachusetts General Hospital, Boston, MA.
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Peter M. Sadow
Massachusetts General Hospital, Boston, MA.
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Gilbert H. Daniels
Massachusetts General Hospital, Boston, MA.
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DOI: 10.1158/1538-7445.AM2013-1191 Published April 2013
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Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC

Abstract

Thyroid cancer is the most common endocrine malignancy and it accounts for the largest fraction of endocrine cancer-related deaths. The accurate classification of well-differentiated thyroid tumors remains a significant challenge that impacts prognosis and therapeutic choices for patients. Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are the most common and the best characterized types of thyroid cancer, being diagnosed in approximately 80% and 15% of patients, respectively. Follicular variant of papillary thyroid carcinoma (FVPTC) is, after classical PTC, the most commonly diagnosed subtype of PTC, accounting for 9% to 22% of PTC cases. FVPTC exhibits some nuclear features of PTC but has a follicular growth pattern. Diagnosis of FVPTC presents a great challenge to pathologists, as these tumors can have distinct prognoses with variable clinical implications. While the incidence/diagnosis of FVPTC is growing in the U.S., the genetic characteristics of the disease remain poorly understood, and there is a need for complementary molecular assays that can help discriminate between the more benign forms of FVPTC and those that will exhibit an aggressive clinical course.

In this study, we performed molecular analysis of 101 FVPTC archival surgical specimens using the SNaPshot multiplexed targeted sequencing platform, to interrogate 90 genetic loci frequently mutated in 21 cancer genes, including the BRAF, HRAS, KRAS, NRAS, PIK3CA and CTNNB1 (β-catenin) oncogenes commonly altered in thyroid cancer. Quantitative reverse transcriptase PCR (qRT-PCR) of cDNA obtained from the same tumors was used to test for the presence of RET/PTC1 and RET/PTC3 gene rearrangements found in PTC, and for PAX8-PPARγ gene fusions characteristic of FTC. We detected mutually exclusive genetic aberrations in 68 (67%) FVTPC. These included 25 (25%) BRAF V600E mutations, 26 (26%) mutations in NRAS (22 Q61R and 4 Q61K), 13 (13%) mutations in HRAS (9 Q61R, 3 Q61K, and 1 G13R) and 3 (3%) KRAS G12V mutations. We identified one (1%) single case of PAX8-PPARγ gene rearrangement and no RET/PTC gene fusions.

Patient medical records and tumor histopathological characteristics will be retrospectively reviewed to determine whether the FVPTC genotype is significantly associated with clinicopathological features of diagnostic and prognostic importance that could help inform therapeutic decisions for this commonly diagnosed endocrine tumor.

Citation Format: Dora Dias-Santagata, David G. McFadden, Lindsay A. Bernardo, Kerry D. Lynch, A. John Iafrate, Peter M. Sadow, Gilbert H. Daniels. Somatic mutation profiling of the follicular variant of papillary thyroid cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1191. doi:10.1158/1538-7445.AM2013-1191

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Cancer Research: 73 (8 Supplement)
April 2013
Volume 73, Issue 8 Supplement
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Abstract 1191: Somatic mutation profiling of the follicular variant of papillary thyroid cancer.
Dora Dias-Santagata, David G. McFadden, Lindsay A. Bernardo, Kerry D. Lynch, A. John Iafrate, Peter M. Sadow and Gilbert H. Daniels
Cancer Res April 15 2013 (73) (8 Supplement) 1191; DOI: 10.1158/1538-7445.AM2013-1191

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Abstract 1191: Somatic mutation profiling of the follicular variant of papillary thyroid cancer.
Dora Dias-Santagata, David G. McFadden, Lindsay A. Bernardo, Kerry D. Lynch, A. John Iafrate, Peter M. Sadow and Gilbert H. Daniels
Cancer Res April 15 2013 (73) (8 Supplement) 1191; DOI: 10.1158/1538-7445.AM2013-1191
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