Detection and molecular characterization of a novel BRAF activated domain mutation in follicular variant of papillary thyroid carcinoma

Libero Santarpia; Steven I. Sherman; Anna Marabotti; Gary L. Clayman; Adel K. El-Naggar

doi:10.1016/j.humpath.2008.11.003

Detection and molecular characterization of a novel BRAF activated domain mutation in follicular variant of papillary thyroid carcinoma

Libero Santarpia, Steven I. Sherman, Anna Marabotti, Gary L. Clayman, Adel K. El-Naggar

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

To assess the mutational status of BRAF in FVPTC, we directly sequenced the genomic DNA of 30 primary FVPTC samples. BRAF mutations were found in only 4 (13%) tumors. We also identified a previously unknown (novel) mutation in the activation kinase domain of the BRAF (A598V), replacing alanine with valine. Functional analysis showed that this mutation led to the up-regulation of the BRAF kinase activity and its downstream signaling factors. The effect of this mutation on the structural formation of the protein is highlighted. Our results confirm the infrequency of BRAF (V600E) mutation in FVPTC and identify a novel (A598V) mutation of this gene.

Original language	English (US)
Pages (from-to)	827-833
Number of pages	7
Journal	Human Pathology
Volume	40
Issue number	6
DOIs	https://doi.org/10.1016/j.humpath.2008.11.003
State	Published - Jun 2009

Keywords

BRAF mutations
Follicular variant papillary thyroid carcinoma
Kinase domain
Modeling

ASJC Scopus subject areas

Pathology and Forensic Medicine

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10.1016/j.humpath.2008.11.003

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title = "Detection and molecular characterization of a novel BRAF activated domain mutation in follicular variant of papillary thyroid carcinoma",

abstract = "To assess the mutational status of BRAF in FVPTC, we directly sequenced the genomic DNA of 30 primary FVPTC samples. BRAF mutations were found in only 4 (13%) tumors. We also identified a previously unknown (novel) mutation in the activation kinase domain of the BRAF (A598V), replacing alanine with valine. Functional analysis showed that this mutation led to the up-regulation of the BRAF kinase activity and its downstream signaling factors. The effect of this mutation on the structural formation of the protein is highlighted. Our results confirm the infrequency of BRAF (V600E) mutation in FVPTC and identify a novel (A598V) mutation of this gene.",

keywords = "BRAF mutations, Follicular variant papillary thyroid carcinoma, Kinase domain, Modeling",

author = "Libero Santarpia and Sherman, {Steven I.} and Anna Marabotti and Clayman, {Gary L.} and El-Naggar, {Adel K.}",

note = "Funding Information: This work was supported in part by the Kenneth D. M{\"u}ller Professorship, National Cancer Institute Specialized Program of Research Excellence grant in head and neck cancer, and the National Cancer Institute grant CA-16672. ",

year = "2009",

month = jun,

doi = "10.1016/j.humpath.2008.11.003",

language = "English (US)",

volume = "40",

pages = "827--833",

journal = "Human Pathology",

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T1 - Detection and molecular characterization of a novel BRAF activated domain mutation in follicular variant of papillary thyroid carcinoma

AU - Santarpia, Libero

AU - Sherman, Steven I.

AU - Marabotti, Anna

AU - Clayman, Gary L.

AU - El-Naggar, Adel K.

N1 - Funding Information: This work was supported in part by the Kenneth D. Müller Professorship, National Cancer Institute Specialized Program of Research Excellence grant in head and neck cancer, and the National Cancer Institute grant CA-16672.

PY - 2009/6

Y1 - 2009/6

N2 - To assess the mutational status of BRAF in FVPTC, we directly sequenced the genomic DNA of 30 primary FVPTC samples. BRAF mutations were found in only 4 (13%) tumors. We also identified a previously unknown (novel) mutation in the activation kinase domain of the BRAF (A598V), replacing alanine with valine. Functional analysis showed that this mutation led to the up-regulation of the BRAF kinase activity and its downstream signaling factors. The effect of this mutation on the structural formation of the protein is highlighted. Our results confirm the infrequency of BRAF (V600E) mutation in FVPTC and identify a novel (A598V) mutation of this gene.

AB - To assess the mutational status of BRAF in FVPTC, we directly sequenced the genomic DNA of 30 primary FVPTC samples. BRAF mutations were found in only 4 (13%) tumors. We also identified a previously unknown (novel) mutation in the activation kinase domain of the BRAF (A598V), replacing alanine with valine. Functional analysis showed that this mutation led to the up-regulation of the BRAF kinase activity and its downstream signaling factors. The effect of this mutation on the structural formation of the protein is highlighted. Our results confirm the infrequency of BRAF (V600E) mutation in FVPTC and identify a novel (A598V) mutation of this gene.

KW - BRAF mutations

KW - Follicular variant papillary thyroid carcinoma

KW - Kinase domain

KW - Modeling

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JO - Human Pathology

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IS - 6

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Detection and molecular characterization of a novel BRAF activated domain mutation in follicular variant of papillary thyroid carcinoma

Abstract

Keywords

ASJC Scopus subject areas

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