Mutation in Genes Encoding Key Functional Groups Additively Increase Mortality in Patients with <i>BRAF<sup>V600E</sup></i>-Mutant Advanced Papillary Thyroid Carcinoma

Mutation in Genes Encoding Key Functional Groups Additively Increase Mortality in Patients with <i>BRAF<sup>V600E</sup></i>-Mutant Advanced Papillary Thyroid Carcinoma

The prognosis of <i>BRAF<sup>V600E</sup></i>-mutant papillary thyroid carcinoma (PTC) ranges from indolent to highly aggressive courses. To better define the genetic diversity of this subtype, we evaluated the survival according to the presence of an additional mutation in ge...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Eyun Song, Meihua Jin, Ahreum Jang, Min Ji Jeon, Dong Eun Song, Hye Jin Yoo, Won Bae Kim, Young Kee Shong, Won Gu Kim
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
papillary thyroid carcinoma
genetic mutation
BRAF
functional groups
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Acceso en línea:https://doaj.org/article/a84d0ba8a0654c78b83d51e726ac5ecd
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:a84d0ba8a0654c78b83d51e726ac5ecd
record_format dspace
spelling oai:doaj.org-article:a84d0ba8a0654c78b83d51e726ac5ecd2021-11-25T17:04:42ZMutation in Genes Encoding Key Functional Groups Additively Increase Mortality in Patients with <i>BRAF<sup>V600E</sup></i>-Mutant Advanced Papillary Thyroid Carcinoma10.3390/cancers132258462072-6694https://doaj.org/article/a84d0ba8a0654c78b83d51e726ac5ecd2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5846https://doaj.org/toc/2072-6694The prognosis of <i>BRAF<sup>V600E</sup></i>-mutant papillary thyroid carcinoma (PTC) ranges from indolent to highly aggressive courses. To better define the genetic diversity of this subtype, we evaluated the survival according to the presence of an additional mutation in genes encoding functional groups (FGs) in <i>BRAF<sup>V600E</sup></i>-mutant advanced PTC patients. Targeted next-generation sequencing was performed in primary tumors of 50 <i>BRAF<sup>V600E</sup></i>-mutant PTCs with distant metastasis or aggressive variants. The mutation in genes encoding FGs included alterations in histone methyltransferases, SWI/SNF subunit, and the PI3K/AKT/mTOR pathway. The primary outcome was overall survival (OS). Fifteen patients only had the <i>BRAF<sup>V600E</sup></i>-mutation (group 1), 22 had <i>BRAF<sup>V600E</sup></i> and mutation other than FGs (group 2), and 13 had <i>BRAF<sup>V600E</sup></i> and FG mutation (group 3). OS was significantly lower in patients with FG mutations (<i>p</i> = 0.001) than those without, and group 3 patients had the worst survival (<i>p</i> = 0.004). OS significantly varied among none, one, or two FG mutation sites (<i>p</i> = 0.005). Presence of FG mutation was independently associated with increased mortality (hazard ratio 11.65, 95% confidence interval 1.39–97.58, <i>p</i> = 0.024). Coexistence of mutations in <i>BRAF<sup>V600E</sup></i> and genes encoding FGs was associated with high mortality. Identification of FG mutation in <i>BRAF<sup>V600E</sup></i>-mutant PTCs may be valuable in risk stratifying this subtype.Eyun SongMeihua JinAhreum JangMin Ji JeonDong Eun SongHye Jin YooWon Bae KimYoung Kee ShongWon Gu KimMDPI AGarticlepapillary thyroid carcinomagenetic mutationBRAFfunctional groupsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5846, p 5846 (2021)
institution DOAJ
collection DOAJ
language EN
topic papillary thyroid carcinoma
genetic mutation
BRAF
functional groups
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle papillary thyroid carcinoma
genetic mutation
BRAF
functional groups
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Eyun Song
Meihua Jin
Ahreum Jang
Min Ji Jeon
Dong Eun Song
Hye Jin Yoo
Won Bae Kim
Young Kee Shong
Won Gu Kim
Mutation in Genes Encoding Key Functional Groups Additively Increase Mortality in Patients with <i>BRAF<sup>V600E</sup></i>-Mutant Advanced Papillary Thyroid Carcinoma
description The prognosis of <i>BRAF<sup>V600E</sup></i>-mutant papillary thyroid carcinoma (PTC) ranges from indolent to highly aggressive courses. To better define the genetic diversity of this subtype, we evaluated the survival according to the presence of an additional mutation in genes encoding functional groups (FGs) in <i>BRAF<sup>V600E</sup></i>-mutant advanced PTC patients. Targeted next-generation sequencing was performed in primary tumors of 50 <i>BRAF<sup>V600E</sup></i>-mutant PTCs with distant metastasis or aggressive variants. The mutation in genes encoding FGs included alterations in histone methyltransferases, SWI/SNF subunit, and the PI3K/AKT/mTOR pathway. The primary outcome was overall survival (OS). Fifteen patients only had the <i>BRAF<sup>V600E</sup></i>-mutation (group 1), 22 had <i>BRAF<sup>V600E</sup></i> and mutation other than FGs (group 2), and 13 had <i>BRAF<sup>V600E</sup></i> and FG mutation (group 3). OS was significantly lower in patients with FG mutations (<i>p</i> = 0.001) than those without, and group 3 patients had the worst survival (<i>p</i> = 0.004). OS significantly varied among none, one, or two FG mutation sites (<i>p</i> = 0.005). Presence of FG mutation was independently associated with increased mortality (hazard ratio 11.65, 95% confidence interval 1.39–97.58, <i>p</i> = 0.024). Coexistence of mutations in <i>BRAF<sup>V600E</sup></i> and genes encoding FGs was associated with high mortality. Identification of FG mutation in <i>BRAF<sup>V600E</sup></i>-mutant PTCs may be valuable in risk stratifying this subtype.
format article
author Eyun Song
Meihua Jin
Ahreum Jang
Min Ji Jeon
Dong Eun Song
Hye Jin Yoo
Won Bae Kim
Young Kee Shong
Won Gu Kim
author_facet Eyun Song
Meihua Jin
Ahreum Jang
Min Ji Jeon
Dong Eun Song
Hye Jin Yoo
Won Bae Kim
Young Kee Shong
Won Gu Kim
author_sort Eyun Song
title Mutation in Genes Encoding Key Functional Groups Additively Increase Mortality in Patients with <i>BRAF<sup>V600E</sup></i>-Mutant Advanced Papillary Thyroid Carcinoma
title_short Mutation in Genes Encoding Key Functional Groups Additively Increase Mortality in Patients with <i>BRAF<sup>V600E</sup></i>-Mutant Advanced Papillary Thyroid Carcinoma
title_full Mutation in Genes Encoding Key Functional Groups Additively Increase Mortality in Patients with <i>BRAF<sup>V600E</sup></i>-Mutant Advanced Papillary Thyroid Carcinoma
title_fullStr Mutation in Genes Encoding Key Functional Groups Additively Increase Mortality in Patients with <i>BRAF<sup>V600E</sup></i>-Mutant Advanced Papillary Thyroid Carcinoma
title_full_unstemmed Mutation in Genes Encoding Key Functional Groups Additively Increase Mortality in Patients with <i>BRAF<sup>V600E</sup></i>-Mutant Advanced Papillary Thyroid Carcinoma
title_sort mutation in genes encoding key functional groups additively increase mortality in patients with <i>braf<sup>v600e</sup></i>-mutant advanced papillary thyroid carcinoma
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/a84d0ba8a0654c78b83d51e726ac5ecd
work_keys_str_mv AT eyunsong mutationingenesencodingkeyfunctionalgroupsadditivelyincreasemortalityinpatientswithibrafsupv600esupimutantadvancedpapillarythyroidcarcinoma
AT meihuajin mutationingenesencodingkeyfunctionalgroupsadditivelyincreasemortalityinpatientswithibrafsupv600esupimutantadvancedpapillarythyroidcarcinoma
AT ahreumjang mutationingenesencodingkeyfunctionalgroupsadditivelyincreasemortalityinpatientswithibrafsupv600esupimutantadvancedpapillarythyroidcarcinoma
AT minjijeon mutationingenesencodingkeyfunctionalgroupsadditivelyincreasemortalityinpatientswithibrafsupv600esupimutantadvancedpapillarythyroidcarcinoma
AT dongeunsong mutationingenesencodingkeyfunctionalgroupsadditivelyincreasemortalityinpatientswithibrafsupv600esupimutantadvancedpapillarythyroidcarcinoma
AT hyejinyoo mutationingenesencodingkeyfunctionalgroupsadditivelyincreasemortalityinpatientswithibrafsupv600esupimutantadvancedpapillarythyroidcarcinoma
AT wonbaekim mutationingenesencodingkeyfunctionalgroupsadditivelyincreasemortalityinpatientswithibrafsupv600esupimutantadvancedpapillarythyroidcarcinoma
AT youngkeeshong mutationingenesencodingkeyfunctionalgroupsadditivelyincreasemortalityinpatientswithibrafsupv600esupimutantadvancedpapillarythyroidcarcinoma
AT wongukim mutationingenesencodingkeyfunctionalgroupsadditivelyincreasemortalityinpatientswithibrafsupv600esupimutantadvancedpapillarythyroidcarcinoma
_version_ 1718412732681682944

Ejemplares similares