Ilda Patrícia Tavares da Silva Ribeiro Head and Neck Squamous Cell Carcinoma: integrating genomic, epigenetic and transcriptomic data - from bench to clinical applications Tese de doutoramento do Programa Interuniversitário de Doutoramento em Envelhecimento e Doenças Crónicas, orientada pela Senhora Professora Isabel Marques Carreira e pelo Senhor Professor Rui Manuel Reis e Coorientada pela Senhora Professora Joana Barbosa de Melo, o grau é conferido pelas Faculdade de Medicina da Universidade de Coimbra, Faculdade de Ciências Médicas da Universidade Nova de Lisboa e Escola de Ciências da Saúde da Universidade do Minho, e é apresentada à Faculdade de Medicina da Universidade de Coimbra. Julho 2017 Institutions and Funding The presented research study involved the following institutions and funding: i Publications The following original articles and abstracts have been published (or submitted) in peer-scientific journals, within the scope of the present work. Book Chapters Ilda P. Ribeiro, Joana B. Melo, Isabel M. Carreira (2017). High -Throughput Genomic Approaches for Head and Neck Cancer: Towards Molecular Biomarkers and Targeted Therapies, In: Head and Neck Cancer, Avid Science, Telangana, India, 2017. 2-31 Original articles (in chronological order) Published 1. 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, 2017. 10(13):2-9 doi: 10.1186/s13039-017-0310-z (Chapter 3.4.3) 2. Ilda P. Ribeiro, Francisco Caramelo, Francisco Marques, Ana Domingues, Margarida Mesquita, Leonor Barroso, Hugo Prazeres, Maria J. Julião, Isabel P. Baptista, Artur Ferreira, Joana B. Melo, Isabel M. Carreira. WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report. Cellular Oncology, 2016. 39(6):573-582 doi: 10.1007/s13402-016-0293-5 (Chapter 3.1.3) 3. Ilda P. Ribeiro, Leonor Barroso, Francisco Marques, Joana B. Melo, Isabel M. Carreira. Early detection and personalized treatment in oral cancer: the impact of omics approaches. Molecular Cytogenetics, 2016. 9(85):1-7 doi: 10.1186/s13039-016-0293-1 iii 4. Ilda P. Ribeiro, Francisco Marques, Francisco Caramelo, João Pereira, Miguel Patrício, Hugo Prazeres, José Ferrão, Maria J. Julião, Miguel Castelo-Branco, Joana B. Melo, Isabel P. Baptista, Isabel M. Carreira. Genetic gains and losses in oral squamous cell carcinoma: impact on clinical management. Cellular Oncology, 2014. 37(1):29-39 doi:10.1007/s13402-013-0161-5 (Chapter 3.1.1) 5. Ilda P. Ribeiro, Francisco Marques, Francisco Caramelo, José Ferrão, Hugo Prazeres, Maria J. Julião, Widad Rifi, Suvi Savola, Joana B. Melo, Isabel P. Baptista, Isabel M. Carreira. Genetic imbalances detected by Multiplex Ligation-dependent Probe Amplification in a cohort of patients with oral squamous cell carcinoma - the first step towards clinical personalized medicine. Tumor Biology, 2014. 35 (5):4687-4695 doi: 10.1007/s13277-014-1614-9 (Chapter 3.1.2) In Press 1. Ilda P. Ribeiro, Francisco Marques, Leonor Barroso, Joana Rodrigues, Francisco Caramelo, Joana B. Melo, Isabel M. Carreira. Genomic profile of oral squamous cell carcinomas with an adjacent leukoplakia or with an erythroleukoplakia that evolved after the treatment of primary tumor: a report of two cases. Molecular Medicine Reports. (Chapter 3.4.1) 2. Ilda P. Ribeiro, Joana Rodrigues, Alexandra Mascarenhas, Nadezda Kosyakova, Francisco Caramelo, Thomas Liehr, Joana B. Melo, Isabel M. Carreira. Cytogenetic, genomic and epigenetic characterization of HSC-3 tongue cell line, with lymphnode metastasis. Journal of Oral Sciences. (Chapter 3.5.1) Submitted 1. Ilda P. Ribeiro, Francisco Caramelo, Luísa Esteves, Camila Oliveira, Francisco Marques, Leonor Barroso, Joana B. Melo, Isabel M. Carreira. Genomic and epigenetic signatures associated with survival rate in oral squamous cell carcinoma patients. (Chapter 3.1.4) iv 2. Ilda P. Ribeiro, Francisco Caramelo, Luísa Esteves, Joana Menoita, Francisco Marques, Leonor Barroso, Jorge Miguéis, Joana B. Melo, Isabel M. Carreira. Genomic predictive model for recurrence and metastasis development in head and neck squamous cell carcinoma patients. (Chapter 3.2.1) 3. Ilda P. Ribeiro, Isabel M. Carreira, Thomas Liehr, Joana B. Melo. Chromosomal breaks and low copy repeat elements in head and neck squamous cell carcinoma. (Chapter 3.2.2) 4. Ilda P. Ribeiro, Luísa Esteves, Francisco Caramelo, Francisco Marques, Leonor Barroso, Joana B. Melo, Isabel M. Carreira. Expression of HIF3A, HOXA10 and LOX discriminates tumors of the tongue from the floor of the mouth. (Chapter 3.3.1) 5. Ilda P. Ribeiro, Leonor Barroso, Francisco Marques, André Santos, Francisco Caramelo, Maria J. Julião, Joana B. Melo, Isabel M. Carreira. Genomic and epigenetic characterization for the comparison of synchronous bilateral tongue squamous cell carcinomas - a case report. (Chapter 3.4.2) 6. Ilda P. Ribeiro, Joana M. Rodrigues, Alexandra Mascarenhas, Vanessa Marques, Nadezda Kosyakova, Francisco Caramelo, Maria J. Julião, Thomas Liehr, Joana B. Melo, Isabel M. Carreira. (Cyto)genomic and epigenetic characterization of BICR 10 cell line and three new established primary human head and neck squamous cell carcinoma cultures. (Chapter 3.5.2) Peer-Reviewed conference abstracts published on indexed journals 1. Isabel M. Carreira, Ilda P. Ribeiro, Susana I. Ferreira, Alexandra Mascarenhas, Joana Rodrigues, Vanessa Marques, Cláudia Pais, Francisco Marques, Joana B. Melo. From the establishment of primary culture cell v lines of oral squamous cell carcinoma to the identification of complex rearrangements. Molecular Cytogenetics, 2017. 10(Suppl1)2.20 2. Ilda P. Ribeiro, Francisco Caramelo, Francisco Marques, André Santos, Leonor Barroso, Margarida Mesquita, Teresa Lopes, Maria J. Julião, Artur Ferreira, Isabel P. Baptista, Joana B. Melo, Isabel M Carreira. Genomic classification of oral squamous cell carcinoma: the role of copy number alterations. European Journal of Human Genetics, Supplement. 2016; 24 (E-Supplement 1): 279 3. Isabel M. Carreira, Ilda P. Ribeiro, Francisco Marques, Francisco Caramelo, André Santos, Maria J. Julião, Isabel P. Baptista, Joana B. Melo. Oral squamous cell carcinoma: can the genes predict a second primary tumor? European Journal of Human Genetics, Supplement. 2016; 24 (E- Supplement 1): 295 4. Ilda P. Ribeiro, Francisco Marques, André Santos, Francisco Caramelo, Isabel P. Baptista, Joana B. Melo, Isabel M. Carreira. Novel regions of gain and loss on chromosome 11 detected in the oral squamous cell carcinoma. Revista Portuguesa de Pneumologia. 2016; 22 (Esp Cong 2):6 5. Ilda P. Ribeiro, Francisco Marques, André Santos, Joana Menoita, Isabel P. Baptista, Isabel M. Carreira, Joana B. Melo. Non-random genomic breakpoints in oral cancer: which characteristic sequence motifs are behind the breaks? Revista Portuguesa de Pneumologia. 2016; 22 (Esp Cong 2):13 6. Ilda P. Ribeiro, Francisco Caramelo, Francisco Marques, Ana Domingues, Alexandra Estevinho, Maria J. Julião, Artur Ferreira, Isabel P. Baptista, Joana B. Melo, Isabel M. Carreira. From oral cancer genetic and epigenetic alterations to clinical outcome prediction. European Journal of Human Genetics. 2015; (Supplement 1): 260 7. Ilda P. Ribeiro, Ana Cainço, Francisco Marques, Francisco Caramelo, Alexandra Estevinho, Maria J. Julião, Joana B. Melo, Artur Ferreira, Isabel P. Baptista, Isabel M. Carreira. Decoding genetic and epigenetic signatures in oral squamous cell carcinoma. Revista Portuguesa de Pneumologia. 2015. 21 (Esp Cong 1):4 vi 8. Ilda P. Ribeiro, Francisco Marques, Francisco Caramelo, Susana I. Ferreira, Luís M. Pires, Joana Rodrigues, Maria J. Julião, Joana B. Melo, Artur Ferreira, Isabel P. Baptista, Isabel M. Carreira. Genome-wide copy number analysis in oral squamous cell carcinoma. Revista Portuguesa de Pneumologia. 2015. 21 (Esp Cong 1):9 9. Ilda P. Ribeiro, Francisco Marques, Susana I. Ferreira, Luís M. Pires, Francisco Caramelo, Maria J. Julião, Joana B. Melo, Isabel P. Baptista, Isabel M. Carreira. The contribution of array-CGH to reveal genomic biomarkers for oral cancer. Revista Portuguesa de Pneumologia. 2014. 20:2-3 10. Ilda P. Ribeiro, Francisco Marques, Francisco Caramelo, José Ferrão, Maria J. Julião, Joana B. Melo, Isabel P. Baptista, Isabel M. Carreira. Genetic profile of oral cancer as a valuable ally for clinicians. Revista Portuguesa de Pneumologia. 2014. 20:10-11 11. Francisco Marques, Ilda P. Ribeiro, Hugo Prazeres, Maria J. Julião, Isabel P. Baptista, Joana B. Melo, Isabel M. Carreira. HPV and head and neck cancer: guilty or not guilty? Revista Portuguesa de Pneumologia. 2014. 20:11 12. Francisco Marques, Ilda P. Ribeiro, Susana I. Ferreira, José Ferrão, Maria J. Julião, Isabel P. Baptista, Joana B. Melo, Isabel M. Carreira. Head and neck cancer: a heterogeneous disease? Revista Portuguesa de Pneumologia. 2014. 20:11-12 Conference abstract published in conference proceedings 1. Ilda P. Ribeiro, Leonor Barroso, Francisco Marques, André Santos, Francisco Caramelo, Maria J. Julião, Joana B. Melo, Isabel M. Carreira. One patient and two synchronous tongue tumors: how genes help to discriminate bilateral carcinomas? Livro de Resumos 20ª Reunião Anual da Sociedade Portuguesa de Genética Humana, Fundação Bissaya Barreto, Coimbra (2016). pp129 vii 2. Ilda P. Ribeiro, André Santos, Francisco