Evidence of Cooperation between Hippo Pathway and RAS Mutation in Thyroid Carcinomas.

Autor: Carneiro TNR; Genetic 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, Brazil., Bim LV; Genetic 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, Brazil., Buzatto VC; Centro de Oncologia Molecular, Hospital Sírio-libanês, Rua Professor Daher Cutait 69, Bela Vista, São Paulo, SP 01308-060, Brazil., Galdeno V; Centro de Oncologia Molecular, Hospital Sírio-libanês, Rua Professor Daher Cutait 69, Bela Vista, São Paulo, SP 01308-060, Brazil., Asprino PF; Centro de Oncologia Molecular, Hospital Sírio-libanês, Rua Professor Daher Cutait 69, Bela Vista, São Paulo, SP 01308-060, Brazil., Lee EA; Division 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, USA., Galante PAF; Centro de Oncologia Molecular, Hospital Sírio-libanês, Rua Professor Daher Cutait 69, Bela Vista, São Paulo, SP 01308-060, Brazil., Cerutti JM; Genetic 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, Brazil.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 May 12; Vol. 13 (10). Date of Electronic Publication: 2021 May 12.
DOI: 10.3390/cancers13102306
Abstrakt: 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. RAS 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 RAS cooperates with other driver mutations to induce tumorigenesis. This study aims to identify genetic alterations or pathways that cooperate with the RAS mutation in the pathogenesis of thyroid cancer. From a cohort of 120 thyroid carcinomas, 11 RAS -mutated samples were identified. The samples were subjected to RNA-Sequencing analyses. The mutation analysis in our eleven RAS -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 RAS -positive samples. We additionally explored the mutational status and expression profiling of 60 RAS -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 RAS -positive thyroid carcinomas. Finally, we suggest a crosstalk between the Hippo and other signaling pathways, such as Wnt and BMP.
Databáze: MEDLINE
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