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Genetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumor

BACKGROUND: The choice of therapeutic modality for oral carcinoma in recurrent or second primary tumors remains controversial, as the treatment modalities available might be reduced by the treatment of the first tumor, and the overall survival is lower when compared with patients with a single or fi...

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Autores principales: Ribeiro, Ilda P., Marques, Francisco, Barroso, Leonor, Miguéis, Jorge, Caramelo, Francisco, Santos, André, Julião, Maria J., Melo, Joana B., Carreira, Isabel M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5387319/
https://www.ncbi.nlm.nih.gov/pubmed/28413448
http://dx.doi.org/10.1186/s13039-017-0310-z
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author Ribeiro, Ilda P.
Marques, Francisco
Barroso, Leonor
Miguéis, Jorge
Caramelo, Francisco
Santos, André
Julião, Maria J.
Melo, Joana B.
Carreira, Isabel M.
author_facet Ribeiro, Ilda P.
Marques, Francisco
Barroso, Leonor
Miguéis, Jorge
Caramelo, Francisco
Santos, André
Julião, Maria J.
Melo, Joana B.
Carreira, Isabel M.
author_sort Ribeiro, Ilda P.
collection PubMed
description BACKGROUND: The choice of therapeutic modality for oral carcinoma in recurrent or second primary tumors remains controversial, as the treatment modalities available might be reduced by the treatment of the first tumor, and the overall survival is lower when compared with patients with a single or first tumor. Identifying biomarkers that predict the risk of relapse and the response to treatment is an emerging clinical issue. CASE PRESENTATION: A Caucasian 49-years-old man was treated with chemotherapy followed by chemoradiotherapy for a primary left side tongue tumor, achieving a complete response. After 49-months of follow-up, a local recurrence was diagnosed. After 3 months, a second primary tumor at the pharyngoesophageal region was detected. Genomic and epigenetic characterization of these three tumors was performed using array Comparative Genomic Hybridization, Multiplex Ligation-dependent Probe Amplification (MLPA) and Methylation Specific MLPA. RESULTS: The three tumors of this patient shared several imbalances in all chromosomes excluding chromosomes 9, 20 and 22, where genes related to important functional mechanisms of tumorigenesis are mapped. The shared genomic imbalances, such as losses at 1p, 2p, 3p, 4q, 5q, 6q, 7q, 8p, 10p, 11q, 12p, 12q, 13q, 15q, 16p, 16q, 17p, 17q, 18q, 19p, 19q, 21q and Xp and gains at 3q, 7q, 14q and 15q showed a common clonal origin for the diagnosed relapses. We identified some chromosomal imbalances and genes mapped in the chromosomes 2, 3, 4, 6, 7, 11, 14, 17, 18 and 22 as putative linked to chemoradioresistance and chemoradiosensitivity. We also observed that gains in short arm of chromosomes 6, 7, 8 and 18 were acquired after treatment of the primary tumor. We identified losses of VHL gene and promoter methylation of WT1 and GATA5 genes, as predictors of relapses. CONCLUSIONS: A common clonal origin for the diagnosed relapses was observed and we identified some putative candidate biomarkers of prognosis, relapse risk and treatment response that could guide the development of management strategies for these patients.
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spelling pubmed-53873192017-04-14 Genetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumor Ribeiro, Ilda P. Marques, Francisco Barroso, Leonor Miguéis, Jorge Caramelo, Francisco Santos, André Julião, Maria J. Melo, Joana B. Carreira, Isabel M. Mol Cytogenet Case Report BACKGROUND: The choice of therapeutic modality for oral carcinoma in recurrent or second primary tumors remains controversial, as the treatment modalities available might be reduced by the treatment of the first tumor, and the overall survival is lower when compared with patients with a single or first tumor. Identifying biomarkers that predict the risk of relapse and the response to treatment is an emerging clinical issue. CASE PRESENTATION: A Caucasian 49-years-old man was treated with chemotherapy followed by chemoradiotherapy for a primary left side tongue tumor, achieving a complete response. After 49-months of follow-up, a local recurrence was diagnosed. After 3 months, a second primary tumor at the pharyngoesophageal region was detected. Genomic and epigenetic characterization of these three tumors was performed using array Comparative Genomic Hybridization, Multiplex Ligation-dependent Probe Amplification (MLPA) and Methylation Specific MLPA. RESULTS: The three tumors of this patient shared several imbalances in all chromosomes excluding chromosomes 9, 20 and 22, where genes related to important functional mechanisms of tumorigenesis are mapped. The shared genomic imbalances, such as losses at 1p, 2p, 3p, 4q, 5q, 6q, 7q, 8p, 10p, 11q, 12p, 12q, 13q, 15q, 16p, 16q, 17p, 17q, 18q, 19p, 19q, 21q and Xp and gains at 3q, 7q, 14q and 15q showed a common clonal origin for the diagnosed relapses. We identified some chromosomal imbalances and genes mapped in the chromosomes 2, 3, 4, 6, 7, 11, 14, 17, 18 and 22 as putative linked to chemoradioresistance and chemoradiosensitivity. We also observed that gains in short arm of chromosomes 6, 7, 8 and 18 were acquired after treatment of the primary tumor. We identified losses of VHL gene and promoter methylation of WT1 and GATA5 genes, as predictors of relapses. CONCLUSIONS: A common clonal origin for the diagnosed relapses was observed and we identified some putative candidate biomarkers of prognosis, relapse risk and treatment response that could guide the development of management strategies for these patients. BioMed Central 2017-04-11 /pmc/articles/PMC5387319/ /pubmed/28413448 http://dx.doi.org/10.1186/s13039-017-0310-z Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Case Report
Ribeiro, Ilda P.
Marques, Francisco
Barroso, Leonor
Miguéis, Jorge
Caramelo, Francisco
Santos, André
Julião, Maria J.
Melo, Joana B.
Carreira, Isabel M.
Genetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumor
title Genetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumor
title_full Genetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumor
title_fullStr Genetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumor
title_full_unstemmed Genetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumor
title_short Genetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumor
title_sort genetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumor
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5387319/
https://www.ncbi.nlm.nih.gov/pubmed/28413448
http://dx.doi.org/10.1186/s13039-017-0310-z
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