Evidence of Cooperation between Hippo Pathway and <i>RAS</i> Mutation in Thyroid Carcinomas
Thyroid cancer incidences have been steadily increasing worldwide and are projected to become the fourth leading cancer diagnosis by 2030. Improved diagnosis and prognosis predictions for this type of cancer depend on understanding its genetic bases and disease biology. <i>RAS</i> mutati...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-05-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/10/2306 |
| _version_ | 1797534537398353920 |
|---|---|
| author | Thaise Nayane Ribeiro Carneiro Larissa Valdemarin Bim Vanessa Candiotti Buzatto Vanessa Galdeno Paula Fontes Asprino Eunjung Alice Lee Pedro Alexandre Favoretto Galante Janete Maria Cerutti |
| author_facet | Thaise Nayane Ribeiro Carneiro Larissa Valdemarin Bim Vanessa Candiotti Buzatto Vanessa Galdeno Paula Fontes Asprino Eunjung Alice Lee Pedro Alexandre Favoretto Galante Janete Maria Cerutti |
| author_sort | Thaise Nayane Ribeiro Carneiro |
| collection | DOAJ |
| description | Thyroid cancer incidences have been steadily increasing worldwide and are projected to become the fourth leading cancer diagnosis by 2030. Improved diagnosis and prognosis predictions for this type of cancer depend on understanding its genetic bases and disease biology. <i>RAS</i> mutations have been found in a wide range of thyroid tumors, from benign to aggressive thyroid carcinomas. Based on that and in vivo studies, it has been suggested that <i>RAS</i> cooperates with other driver mutations to induce tumorigenesis. This study aims to identify genetic alterations or pathways that cooperate with the <i>RAS</i> mutation in the pathogenesis of thyroid cancer. From a cohort of 120 thyroid carcinomas, 11 <i>RAS</i>-mutated samples were identified. The samples were subjected to RNA-Sequencing analyses. The mutation analysis in our eleven <i>RAS</i>-positive cases uncovered that four genes that belong to the Hippo pathway were mutated. The gene expression analysis revealed that this pathway was dysregulated in the <i>RAS</i>-positive samples. We additionally explored the mutational status and expression profiling of 60 <i>RAS</i>-positive papillary thyroid carcinomas (PTC) from The Cancer Genome Atlas (TCGA) cohort. Altogether, the mutational landscape and pathway enrichment analysis (gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genome (KEGG)) detected the Hippo pathway as dysregulated in <i>RAS</i>-positive thyroid carcinomas. Finally, we suggest a crosstalk between the Hippo and other signaling pathways, such as Wnt and BMP. |
| first_indexed | 2024-03-10T11:30:54Z |
| format | Article |
| id | doaj.art-aae12861eee14a30b3a213926f50366b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T11:30:54Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-aae12861eee14a30b3a213926f50366b2023-11-21T19:16:04ZengMDPI AGCancers2072-66942021-05-011310230610.3390/cancers13102306Evidence of Cooperation between Hippo Pathway and <i>RAS</i> Mutation in Thyroid CarcinomasThaise Nayane Ribeiro Carneiro0Larissa Valdemarin Bim1Vanessa Candiotti Buzatto2Vanessa Galdeno3Paula Fontes Asprino4Eunjung Alice Lee5Pedro Alexandre Favoretto Galante6Janete Maria Cerutti7Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Pedro de Toledo 669, 11 Andar, São Paulo, SP 04039-032, BrazilGenetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Pedro de Toledo 669, 11 Andar, São Paulo, SP 04039-032, BrazilCentro de Oncologia Molecular, Hospital Sírio-libanês, Rua Professor Daher Cutait 69, Bela Vista, São Paulo, SP 01308-060, BrazilCentro de Oncologia Molecular, Hospital Sírio-libanês, Rua Professor Daher Cutait 69, Bela Vista, São Paulo, SP 01308-060, BrazilCentro de Oncologia Molecular, Hospital Sírio-libanês, Rua Professor Daher Cutait 69, Bela Vista, São Paulo, SP 01308-060, BrazilDivision of Genetics and Genomics, Boston Children’s Hospital and Harvard Medical School, 3 Blackfan Circle, CLS (Center for Life Science) Building 15th Floor, Office 15020 | Lab 15072, Boston, MA 02115, USACentro de Oncologia Molecular, Hospital Sírio-libanês, Rua Professor Daher Cutait 69, Bela Vista, São Paulo, SP 01308-060, BrazilGenetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Pedro de Toledo 669, 11 Andar, São Paulo, SP 04039-032, BrazilThyroid cancer incidences have been steadily increasing worldwide and are projected to become the fourth leading cancer diagnosis by 2030. Improved diagnosis and prognosis predictions for this type of cancer depend on understanding its genetic bases and disease biology. <i>RAS</i> mutations have been found in a wide range of thyroid tumors, from benign to aggressive thyroid carcinomas. Based on that and in vivo studies, it has been suggested that <i>RAS</i> cooperates with other driver mutations to induce tumorigenesis. This study aims to identify genetic alterations or pathways that cooperate with the <i>RAS</i> mutation in the pathogenesis of thyroid cancer. From a cohort of 120 thyroid carcinomas, 11 <i>RAS</i>-mutated samples were identified. The samples were subjected to RNA-Sequencing analyses. The mutation analysis in our eleven <i>RAS</i>-positive cases uncovered that four genes that belong to the Hippo pathway were mutated. The gene expression analysis revealed that this pathway was dysregulated in the <i>RAS</i>-positive samples. We additionally explored the mutational status and expression profiling of 60 <i>RAS</i>-positive papillary thyroid carcinomas (PTC) from The Cancer Genome Atlas (TCGA) cohort. Altogether, the mutational landscape and pathway enrichment analysis (gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genome (KEGG)) detected the Hippo pathway as dysregulated in <i>RAS</i>-positive thyroid carcinomas. Finally, we suggest a crosstalk between the Hippo and other signaling pathways, such as Wnt and BMP.https://www.mdpi.com/2072-6694/13/10/2306thyroid cancer<i>RAS</i> mutationRNA-SeqTCGAHippo pathway |
| spellingShingle | Thaise Nayane Ribeiro Carneiro Larissa Valdemarin Bim Vanessa Candiotti Buzatto Vanessa Galdeno Paula Fontes Asprino Eunjung Alice Lee Pedro Alexandre Favoretto Galante Janete Maria Cerutti Evidence of Cooperation between Hippo Pathway and <i>RAS</i> Mutation in Thyroid Carcinomas Cancers thyroid cancer <i>RAS</i> mutation RNA-Seq TCGA Hippo pathway |
| title | Evidence of Cooperation between Hippo Pathway and <i>RAS</i> Mutation in Thyroid Carcinomas |
| title_full | Evidence of Cooperation between Hippo Pathway and <i>RAS</i> Mutation in Thyroid Carcinomas |
| title_fullStr | Evidence of Cooperation between Hippo Pathway and <i>RAS</i> Mutation in Thyroid Carcinomas |
| title_full_unstemmed | Evidence of Cooperation between Hippo Pathway and <i>RAS</i> Mutation in Thyroid Carcinomas |
| title_short | Evidence of Cooperation between Hippo Pathway and <i>RAS</i> Mutation in Thyroid Carcinomas |
| title_sort | evidence of cooperation between hippo pathway and i ras i mutation in thyroid carcinomas |
| topic | thyroid cancer <i>RAS</i> mutation RNA-Seq TCGA Hippo pathway |
| url | https://www.mdpi.com/2072-6694/13/10/2306 |
| work_keys_str_mv | AT thaisenayaneribeirocarneiro evidenceofcooperationbetweenhippopathwayandirasimutationinthyroidcarcinomas AT larissavaldemarinbim evidenceofcooperationbetweenhippopathwayandirasimutationinthyroidcarcinomas AT vanessacandiottibuzatto evidenceofcooperationbetweenhippopathwayandirasimutationinthyroidcarcinomas AT vanessagaldeno evidenceofcooperationbetweenhippopathwayandirasimutationinthyroidcarcinomas AT paulafontesasprino evidenceofcooperationbetweenhippopathwayandirasimutationinthyroidcarcinomas AT eunjungalicelee evidenceofcooperationbetweenhippopathwayandirasimutationinthyroidcarcinomas AT pedroalexandrefavorettogalante evidenceofcooperationbetweenhippopathwayandirasimutationinthyroidcarcinomas AT janetemariacerutti evidenceofcooperationbetweenhippopathwayandirasimutationinthyroidcarcinomas |