Genetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumor
Abstract 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 sing...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-04-01
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| Series: | Molecular Cytogenetics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13039-017-0310-z |
| _version_ | 1798044130986688512 |
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| author | Ilda P. Ribeiro Francisco Marques Leonor Barroso Jorge Miguéis Francisco Caramelo André Santos Maria J. Julião Joana B. Melo Isabel M. Carreira |
| author_facet | Ilda P. Ribeiro Francisco Marques Leonor Barroso Jorge Miguéis Francisco Caramelo André Santos Maria J. Julião Joana B. Melo Isabel M. Carreira |
| author_sort | Ilda P. Ribeiro |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T22:58:48Z |
| format | Article |
| id | doaj.art-d2d2e095cd334a5384d6549094e7b322 |
| institution | Directory Open Access Journal |
| issn | 1755-8166 |
| language | English |
| last_indexed | 2024-04-11T22:58:48Z |
| publishDate | 2017-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cytogenetics |
| spelling | doaj.art-d2d2e095cd334a5384d6549094e7b3222022-12-22T03:58:16ZengBMCMolecular Cytogenetics1755-81662017-04-011011910.1186/s13039-017-0310-zGenetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumorIlda P. Ribeiro0Francisco Marques1Leonor Barroso2Jorge Miguéis3Francisco Caramelo4André Santos5Maria J. Julião6Joana B. Melo7Isabel M. Carreira8Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of CoimbraCIMAGO - Center of Investigation on Environment Genetics and Oncobiology - Faculty of Medicine, University of CoimbraMaxillofacial Surgery Department, Coimbra Hospital and University Centre, CHUCDepartment of Otorhinolaryngology - Head and Neck Surgery, Coimbra Hospital and University Centre, CHUCLaboratory of Biostatistics and Medical Informatics, IBILI - Faculty of Medicine, University of CoimbraCytogenetics and Genomics Laboratory, Faculty of Medicine, University of CoimbraDepartment of Pathology, Coimbra Hospital and University Centre, CHUCCytogenetics and Genomics Laboratory, Faculty of Medicine, University of CoimbraCytogenetics and Genomics Laboratory, Faculty of Medicine, University of CoimbraAbstract 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.http://link.springer.com/article/10.1186/s13039-017-0310-zRecurrenceSecond primary tumorGenetic and epigenetic profileOral cancerChemoradioresistance |
| spellingShingle | Ilda P. Ribeiro Francisco Marques Leonor Barroso Jorge Miguéis Francisco Caramelo André Santos Maria J. Julião Joana B. Melo Isabel M. Carreira Genetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumor Molecular Cytogenetics Recurrence Second primary tumor Genetic and epigenetic profile Oral cancer Chemoradioresistance |
| 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 | Recurrence Second primary tumor Genetic and epigenetic profile Oral cancer Chemoradioresistance |
| url | http://link.springer.com/article/10.1186/s13039-017-0310-z |
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