BACKGROUND: BRAFV600E is the most common mutation in papillary thyroid carcinoma (PTC) and can be associated with aggressive disease. Previously, a highly sensitive blood RNA-based BRAFV600E assay was reported. The objective of this study was to assess the correlation of BRAFV600E circulating tumor RNA levels with surgical and medical treatment. METHODS: Circulating BRAFV600E levels were assessed in (i) a murine model of undifferentiated (anaplastic) thyroid carcinoma with known BRAFV600E mutation undergoing BRAFV600E-inhibitor (BRAFi) treatment, and (ii) in 111 patients enrolled prior to thyroidectomy (n = 86) or treatment of advanced recurrent or metastatic PTC (n = 25). Blood samples were drawn for BRAFV600E analysis before and after treatment. Testing characteristics were assessed and positivity criteria optimized. Changes in blood BRAFV600E values were assessed and compared to clinical characteristics and response to therapy. RESULTS: In a murine model of anaplastic thyroid carcinoma with BRAFV600E mutation, blood BRAFV600E RNA correlated with tumor volume in animals treated with BRAFi. In tissue BRAFV600E-positive (n = 36) patients undergoing initial surgery for PTC, blood BRAFV600E levels declined postoperatively (median 370.0-178.5 fg/ng; p = 0.002). In four patients with metastatic or poorly differentiated thyroid carcinoma receiving targeted therapies, blood BRAFV600E declined following therapy and corresponded with radiographic evidence of partial response or stable disease. CONCLUSIONS: This study shows the correlation of blood BRAFV600E levels in response to treatment in both an established animal model of thyroid cancer and in patients with BRAFV600E-positive tumors with all stages of disease. This assay represents an alternative biomarker in patients with positive thyroglobulin antibodies, and tumors, which do not express thyroglobulin.
BACKGROUND:BRAFV600E is the most common mutation in papillary thyroid carcinoma (PTC) and can be associated with aggressive disease. Previously, a highly sensitive blood RNA-based BRAFV600E assay was reported. The objective of this study was to assess the correlation of BRAFV600E circulating tumor RNA levels with surgical and medical treatment. METHODS: Circulating BRAFV600E levels were assessed in (i) a murine model of undifferentiated (anaplastic) thyroid carcinoma with known BRAFV600E mutation undergoing BRAFV600E-inhibitor (BRAFi) treatment, and (ii) in 111 patients enrolled prior to thyroidectomy (n = 86) or treatment of advanced recurrent or metastatic PTC (n = 25). Blood samples were drawn for BRAFV600E analysis before and after treatment. Testing characteristics were assessed and positivity criteria optimized. Changes in blood BRAFV600E values were assessed and compared to clinical characteristics and response to therapy. RESULTS: In a murine model of anaplastic thyroid carcinoma with BRAFV600E mutation, blood BRAFV600E RNA correlated with tumor volume in animals treated with BRAFi. In tissue BRAFV600E-positive (n = 36) patients undergoing initial surgery for PTC, blood BRAFV600E levels declined postoperatively (median 370.0-178.5 fg/ng; p = 0.002). In four patients with metastatic or poorly differentiated thyroid carcinoma receiving targeted therapies, blood BRAFV600E declined following therapy and corresponded with radiographic evidence of partial response or stable disease. CONCLUSIONS: This study shows the correlation of blood BRAFV600E levels in response to treatment in both an established animal model of thyroid cancer and in patients with BRAFV600E-positive tumors with all stages of disease. This assay represents an alternative biomarker in patients with positive thyroglobulin antibodies, and tumors, which do not express thyroglobulin.
Authors: Tae Hyuk Kim; Young Joo Park; Jung Ah Lim; Hwa Young Ahn; Eun Kyung Lee; You Jin Lee; Kyung Won Kim; Seo Kyung Hahn; Yeo Kyu Youn; Kwang Hyun Kim; Bo Youn Cho; Do Joon Park Journal: Cancer Date: 2011-08-31 Impact factor: 6.860
Authors: G A Lupoli; O E Okosieme; C Evans; P M Clark; A J Pickett; L D K E Premawardhana; G Lupoli; J H Lazarus Journal: J Clin Endocrinol Metab Date: 2015-01 Impact factor: 5.958
Authors: Martin Schlumberger; Makoto Tahara; Lori J Wirth; Bruce Robinson; Marcia S Brose; Rossella Elisei; Mouhammed Amir Habra; Kate Newbold; Manisha H Shah; Ana O Hoff; Andrew G Gianoukakis; Naomi Kiyota; Matthew H Taylor; Sung-Bae Kim; Monika K Krzyzanowska; Corina E Dutcus; Begoña de las Heras; Junming Zhu; Steven I Sherman Journal: N Engl J Med Date: 2015-02-12 Impact factor: 91.245
Authors: Marcia S Brose; Maria E Cabanillas; Ezra E W Cohen; Lori J Wirth; Todd Riehl; Huibin Yue; Steven I Sherman; Eric J Sherman Journal: Lancet Oncol Date: 2016-07-23 Impact factor: 41.316
Authors: Grace C Haser; R Michael Tuttle; Henry K Su; Eran E Alon; Donald Bergman; Victor Bernet; Elise Brett; Rhoda Cobin; Eliza H Dewey; Gerard Doherty; Laura L Dos Reis; Jeffrey Harris; Joshua Klopper; Stephanie L Lee; Robert A Levine; Stephen J Lepore; Ilya Likhterov; Mark A Lupo; Josef Machac; Jeffrey I Mechanick; Saral Mehra; Mira Milas; Lisa A Orloff; Gregory Randolph; Tracey A Revenson; Katherine J Roberts; Douglas S Ross; Meghan E Rowe; Robert C Smallridge; David Terris; Ralph P Tufano; Mark L Urken Journal: Endocr Pract Date: 2016-01-22 Impact factor: 3.443
Authors: Krupal B Patel; Nicholas Cormier; James Fowler; Allison Partridge; Julie Theurer; Morgan Black; Nicole Pinto; John Yoo; Kevin Fung; Danielle MacNeil; William Stecho; Christopher Howlett; Muriel Brackstone; John W Barrett; Anthony Nichols Journal: Int J Endocrinol Date: 2021-08-23 Impact factor: 3.257
Authors: Keith C Bible; Electron Kebebew; James Brierley; Juan P Brito; Maria E Cabanillas; Thomas J Clark; Antonio Di Cristofano; Robert Foote; Thomas Giordano; Jan Kasperbauer; Kate Newbold; Yuri E Nikiforov; Gregory Randolph; M Sara Rosenthal; Anna M Sawka; Manisha Shah; Ashok Shaha; Robert Smallridge; Carol K Wong-Clark Journal: Thyroid Date: 2021-03 Impact factor: 6.568