Establishment and characterization of a new patient-derived anaplastic thyroid cancer cell line (C3948), obtained through fine-needle aspiration cytology

Ana T. Pinto, Marta Pojo, Joana Simões-Pereira, Ruben Roque, Ana Saramago, Lúcia Roque, Carmo Martins, Saudade André, José Cabeçadas, Valeriano Leite, Branca M. Cavaco

Research output: Contribution to journalArticle

Abstract

Purpose: Anaplastic thyroid cancer (ATC) is among the most aggressive and unresectable tumors, presenting a bad prognosis. A better comprehension of the functional and molecular mechanisms behind the aggressiveness of this cancer, as well as new biomarkers for aggressiveness, prognosis, and response to therapy are required. However, owing to their irresectability, ATC tissue is not always accessible. Here we describe the establishment and characterization of a new patient-derived cell line, obtained from an unresectable ATC through fine-needle aspiration cytology (FNAC). Methods: The morphology, expression of epithelial and thyroid markers, cytogenetic, mutational and gene expression profiles, doubling time, and drug-resistance profile of the new cell line, designated C3948, were investigated using several methodologies: immunostaining, karyotype analysis, comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), next-generation sequencing (NGS), Sanger sequencing, gene expression microarrays, cell counting, and IC50 determination. Results: Results indicate that C3948 cell line has a histological phenotype representative of original ATC cells and a completely aberrant karyotype with many chromosomal losses and gains; harbors mutated TP53, STK11, and DIS3L2 genes; presents a gene expression profile similar to C643 ATC commercial cell line, but with some unique alterations; has a doubling time similar to C643; and the IC50 profile for paclitaxel, doxorubicin, and cisplatin is similar to C643, although higher for cisplatin. Conclusions: These observations are consistent with a typical ATC cell profile, supporting C3948 cell line as a novel preclinical model, and FNAC as a useful approach to better study anaplastic thyroid cancer, including testing of new anticancer therapies.

Original languageEnglish
JournalEndocrine
DOIs
Publication statusPublished - 1 Jan 2019

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Fine Needle Biopsy
Cell Biology
Cell Line
Karyotype
Transcriptome
Inhibitory Concentration 50
Comparative Genomic Hybridization
Anaplastic Thyroid Carcinoma
Fluorescence In Situ Hybridization
Drug Resistance
Cytogenetics
Doxorubicin
Cisplatin
In Situ Hybridization
Neoplasms
Thyroid Gland
Biomarkers
Phenotype
Gene Expression
Therapeutics

Keywords

  • Anaplastic thyroid cancer
  • Cytogenetic techniques
  • Fine-needle aspiration cytology
  • Genetic profile
  • Molecular biology
  • Tumor cell line

Cite this

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title = "Establishment and characterization of a new patient-derived anaplastic thyroid cancer cell line (C3948), obtained through fine-needle aspiration cytology",
abstract = "Purpose: Anaplastic thyroid cancer (ATC) is among the most aggressive and unresectable tumors, presenting a bad prognosis. A better comprehension of the functional and molecular mechanisms behind the aggressiveness of this cancer, as well as new biomarkers for aggressiveness, prognosis, and response to therapy are required. However, owing to their irresectability, ATC tissue is not always accessible. Here we describe the establishment and characterization of a new patient-derived cell line, obtained from an unresectable ATC through fine-needle aspiration cytology (FNAC). Methods: The morphology, expression of epithelial and thyroid markers, cytogenetic, mutational and gene expression profiles, doubling time, and drug-resistance profile of the new cell line, designated C3948, were investigated using several methodologies: immunostaining, karyotype analysis, comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), next-generation sequencing (NGS), Sanger sequencing, gene expression microarrays, cell counting, and IC50 determination. Results: Results indicate that C3948 cell line has a histological phenotype representative of original ATC cells and a completely aberrant karyotype with many chromosomal losses and gains; harbors mutated TP53, STK11, and DIS3L2 genes; presents a gene expression profile similar to C643 ATC commercial cell line, but with some unique alterations; has a doubling time similar to C643; and the IC50 profile for paclitaxel, doxorubicin, and cisplatin is similar to C643, although higher for cisplatin. Conclusions: These observations are consistent with a typical ATC cell profile, supporting C3948 cell line as a novel preclinical model, and FNAC as a useful approach to better study anaplastic thyroid cancer, including testing of new anticancer therapies.",
keywords = "Anaplastic thyroid cancer, Cytogenetic techniques, Fine-needle aspiration cytology, Genetic profile, Molecular biology, Tumor cell line",
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Establishment and characterization of a new patient-derived anaplastic thyroid cancer cell line (C3948), obtained through fine-needle aspiration cytology. / Pinto, Ana T.; Pojo, Marta; Simões-Pereira, Joana; Roque, Ruben; Saramago, Ana; Roque, Lúcia; Martins, Carmo; André, Saudade; Cabeçadas, José; Leite, Valeriano; Cavaco, Branca M.

In: Endocrine, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Establishment and characterization of a new patient-derived anaplastic thyroid cancer cell line (C3948), obtained through fine-needle aspiration cytology

AU - Pinto, Ana T.

AU - Pojo, Marta

AU - Simões-Pereira, Joana

AU - Roque, Ruben

AU - Saramago, Ana

AU - Roque, Lúcia

AU - Martins, Carmo

AU - André, Saudade

AU - Cabeçadas, José

AU - Leite, Valeriano

AU - Cavaco, Branca M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: Anaplastic thyroid cancer (ATC) is among the most aggressive and unresectable tumors, presenting a bad prognosis. A better comprehension of the functional and molecular mechanisms behind the aggressiveness of this cancer, as well as new biomarkers for aggressiveness, prognosis, and response to therapy are required. However, owing to their irresectability, ATC tissue is not always accessible. Here we describe the establishment and characterization of a new patient-derived cell line, obtained from an unresectable ATC through fine-needle aspiration cytology (FNAC). Methods: The morphology, expression of epithelial and thyroid markers, cytogenetic, mutational and gene expression profiles, doubling time, and drug-resistance profile of the new cell line, designated C3948, were investigated using several methodologies: immunostaining, karyotype analysis, comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), next-generation sequencing (NGS), Sanger sequencing, gene expression microarrays, cell counting, and IC50 determination. Results: Results indicate that C3948 cell line has a histological phenotype representative of original ATC cells and a completely aberrant karyotype with many chromosomal losses and gains; harbors mutated TP53, STK11, and DIS3L2 genes; presents a gene expression profile similar to C643 ATC commercial cell line, but with some unique alterations; has a doubling time similar to C643; and the IC50 profile for paclitaxel, doxorubicin, and cisplatin is similar to C643, although higher for cisplatin. Conclusions: These observations are consistent with a typical ATC cell profile, supporting C3948 cell line as a novel preclinical model, and FNAC as a useful approach to better study anaplastic thyroid cancer, including testing of new anticancer therapies.

AB - Purpose: Anaplastic thyroid cancer (ATC) is among the most aggressive and unresectable tumors, presenting a bad prognosis. A better comprehension of the functional and molecular mechanisms behind the aggressiveness of this cancer, as well as new biomarkers for aggressiveness, prognosis, and response to therapy are required. However, owing to their irresectability, ATC tissue is not always accessible. Here we describe the establishment and characterization of a new patient-derived cell line, obtained from an unresectable ATC through fine-needle aspiration cytology (FNAC). Methods: The morphology, expression of epithelial and thyroid markers, cytogenetic, mutational and gene expression profiles, doubling time, and drug-resistance profile of the new cell line, designated C3948, were investigated using several methodologies: immunostaining, karyotype analysis, comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), next-generation sequencing (NGS), Sanger sequencing, gene expression microarrays, cell counting, and IC50 determination. Results: Results indicate that C3948 cell line has a histological phenotype representative of original ATC cells and a completely aberrant karyotype with many chromosomal losses and gains; harbors mutated TP53, STK11, and DIS3L2 genes; presents a gene expression profile similar to C643 ATC commercial cell line, but with some unique alterations; has a doubling time similar to C643; and the IC50 profile for paclitaxel, doxorubicin, and cisplatin is similar to C643, although higher for cisplatin. Conclusions: These observations are consistent with a typical ATC cell profile, supporting C3948 cell line as a novel preclinical model, and FNAC as a useful approach to better study anaplastic thyroid cancer, including testing of new anticancer therapies.

KW - Anaplastic thyroid cancer

KW - Cytogenetic techniques

KW - Fine-needle aspiration cytology

KW - Genetic profile

KW - Molecular biology

KW - Tumor cell line

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