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Perfiles De Expresión Génica De Los Tumores De Mama Hereditarios

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Perfiles De Expresión Génica De Los Tumores De Mama Hereditarios UNIVERSIDAD AUTÓNOMA DE MADRID Perfiles de expresión génica de los tumores de mama hereditarios Tesis doctoral que presenta para optar al título de Doctor por la Universidad Autónoma de Madrid el Licenciado en Biología Ricardo Ramires Fernández Madrid, diciembre de 2009 Tesis Doctoral dirigida por la Doctora Ana Osorio Cabrero, Investigadora del Programa de Genética del Cáncer Humano del Centro Nacional de Investigaciones Oncológicas Dr. Javier Benítez, Director del Programa de Genética del Cáncer Humano del Centro Nacional de Investigaciones Oncológicas (CNIO) y Profesor Honorario del Departamento de Biología Molecular de la Universidad Autónoma de Madrid, como Tutor, CERTIFICA: Que Don Ricardo Ramires Fernández, Licenciado en Biología por la Universidade Católica de Pelotas ‐ Brasil, ha realizado la presente Tesis Doctoral “Perfiles de expresión génica de los tumores de mama hereditarios” y que a su juicio reúne plenamente todos los requisitos necesarios para optar al Grado de Doctor en Biología Molecular, a cuyos efectos será presentado en la Universidad Autónoma de Madrid. El trabajo ha sido realizado bajo su supervisión, autorizando su presentación ante el Tribunal Calificador. Y para que así conste se extiende el presente certificado, Madrid, diciembre de 2009. Vo Bo del Tutor de la Tesis: Javier Benítez Dra. Ana Osorio Cabrero, Investigadora del Programa de Genética del Cáncer Humano del Centro Nacional de Investigaciones Oncológicas (CNIO) como Directora, CERTIFICA: Que Don Ricardo Ramires Fernández, Licenciado en Biología por la Universidade Católica de Pelotas ‐ Brasil, ha realizado la presente Tesis Doctoral “Perfiles de expresión génica de los tumores de mama hereditarios” y que a su juicio reúne plenamente todos los requisitos necesarios para optar al Grado de Doctor en Biología Molecular, a cuyos efectos será presentado en la Universidad Autónoma de Madrid. El trabajo ha sido realizado bajo su dirección, autorizando su presentación ante el Tribunal Calificador. Y para que así conste se extiende el presente certificado, Madrid, diciembre de 2009. Vo Bo de la Directora de la Tesis: Ana Osorio Cabrero FINANCIACIÓN ESTA TESIS DOCTORAL HA SIDO REALIZADA EN EL GRUPO DE GENÉTICA HUMANA DEL PROGRAMA DE GENÉTICA DEL CÁNCER HUMANO DEL CENTRO NACIONAL DE INVESTIGACIONES ONCOLÓGICAS (CNIO), BAJO LA SUPERVISIÓN DE JAVIER BENÍTEZ ORTIZ Y DIRECCIÓN DE ANA OSORIO CABRERO. LOS SIGUIENTES FONDOS HAN PERMITIDO LA REALIZACIÓN DE LA PRESENTE TESIS DOCTORAL: MARIE CURIE SIXTH FRAMEWORK – ONCOTRAIN CNIO (MEST‐2‐CT‐2004‐6423) EL CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED DE ENFERMEDADES RARAS (CIBERER) FONDOS DE INVESTIGACIONES SANITARIAS (FIS) ‐ FIS PI061090 “HOW BIG WE ARE, WE DON’T FIT IN THE WORLD…” Refrán creado en los últimos cuatro años en el Grupo de Genética Humana del CNIO A mi familia, a aquellos que siguen presentes y a los que ya no están pero que también hacen parte de esta caminata Agradecimientos uando decidi começar a compor esta parte da minha tese provavelmente não tivesse nem iniciado meu período de formação universitária, mas alguma coisa me suscitada ao Q ouvido que seriam muitas linhas, muitos nomes e muito que agradecer e lembrar. Cuando decidi comenzar a componer esta parte de mi tesis, probablemente ni hubiera empezado mi período de formación universitária, pero algo ya me decía que serían muchas líneas, muchos nombres y mucho que agradecer y recordar. É extremamente fácil começar, porém, não o é acabar‐lo. Pai e mãe: vocês que depositaram em mim o maior dos vossos desejos e amor, que fizeram de vossas vidas uma abdicação e doação à causa dos seus filhos. Quantas noites de insônia, sustos ou trabalho maior que levar nove meses junto a vocês. Quantas coisas me propiciaram, quantos sorrisos arrancaram da minha face e quanto exemplo de deram. Das noites e madrugadas de trabalho, tudo para dar‐ me do melhor, brigas pelo teu filho, paciência – e a impaciência – de ensinar‐me o caminho adequado. Da minha personalidade levo um pouco de cada um: a maneira de ver a vida de ti, Pai e a vontade de vencer de ti, Mãe. Vocês quiseram‐me, geraram‐me, alimentaram‐me, criaram‐me e ensinaram‐me que o mais importante, acima de tudo, é a dedicação, a força de querer ser mais e melhor. Vocês são a razão da minha existência. Entretanto, este carinho não é único. Como não falar de meu irmão de sangue. Mano, quanto aprendi contigo e, sobretudo, quanto sigo aprendendo. Desde as típicas brigas entre irmãos até os dias de hoje, que saibas o quanto significas para mim. Es uma pessoa inigualável, de gênio forte e de uma inteligência invejável que espero, geneticamente, poder tê‐la herdado. Desde as tardes que me viste encerrado na frente do computador, escrevendo intermináveis trabalhos da universidade às visitas que te faço sempre que no Brasil estou, ainda es meu grande professor das disciplinas que se chamam moral, caráter e personalidade. À Rita não tenho palavras para agradecer o apoio e o amor de segunda mãe. Amo‐vos minha GRANDE família. Gostaria que vocês soubessem que cada dia é uma nova chance de aprender mais sobre nós mesmos, de se importar mais com os outros, de rir mais do que ríamos, de realizar mais do que pensávamos ser possível, de ser mais do que éramos antes. Reconheço e agradeço o inestimável e importante apoio, amor, compreensão, abdicação e sacrifício que me foi dedicado nesta longa caminhada. Alegrem‐se, pois os méritos desta vitória também são seus! Como não mencionar meus saudosos avôs. Vó Zilma e vô Beto, a memória que mantenho viva de vocês não podia ser mais alegre e fraterna. Desde as primeiras palavras as quais tive o privilegio de ensinar à minha querida avó materna a delinear‐las e sua sábia e singela forma de escutar‐me até as saudosas tardes de filme na casa de meu avô paterno, as tardes com bolinho‐ de‐chuva e as vezes que me buscava no colégio com as mãos dadas, são momentos ímpares que, ainda criança, as recordo e as conservarei por toda minha vida. Por outro lado, o perene apoio da “Vó Zoé” ainda me dá forças a seguir esta batalha no outro lado do Atlântico. Vó, tu es uma das poucas pessoas capazes de entender‐me e perseveraste junto a mim. Neste momento, também te apresentas a um título de Doutora em Ciências da Vida – obrigado por ensinar‐me a ler, escrever e amar as letras que agora levam teu nome. As amizades, juntamente com minha família, são os responsáveis pela minha vitória. Há pessoas com as quais não compartimos laços sangüíneos, mas dividimos o nosso coração. Como não recordar àqueles que me viram crescer ou que cresceram comigo. Ainda, àqueles que não tiveram a oportunidade de seguir seu caminho comigo por terem sido chamados a estar junto ao que denominados Ele, o meu muito obrigado e muitas saudades. Pessoas importantes foram muitas e infelizmente poucas poderei nomear aqui. Lucinha, Cacaio, Carlos e Cadico, como não se lembrar de vocês. Esta infância atravessando a rua, percorrendo o bairro com a bicicleta, os passeios de Fusca e o carinho incondicional. Vocês foram peça‐chave no meu caminho e lhes devo o meu muito obrigado. Marcos, meu padrinho, a família Cardoso é única. Desde o dia cinco de agosto de 1996 me considero uma pessoa com mais sorte. Começamos uma árdua caminhada, de dois amigos que, hoje, seriam nada mais nada menos que grandes irmãos. Foram muitos anos de Colégio Gonzaga, Grupo Jovem, trabalhos de grupo, estudos do “Provão”, alguma vez ou outra no CTG e muitas caipirinhas. Sergio, Valéria, Marcos, Mateus, Bruna, Vó e Marcia, vocês são outra família para mim, uma família que, ainda longe, sabereis que segue ali e que os oferecerei minha gratidão eterna e carinho de filho caçula. Cada um, à sua maneira, contribuiu para que este manuscrito fosse realidade. Há vezes na vida que não sabemos em que caminho estamos nem qual caminho escolher. São nestes momentos que pessoas tão importantes exercem um papel de anjo da guarda. Nestas simples, porém, gratas linhas, dedico esta tese, também, aos meus padrinhos José Américo e Noeli. Foram vários momentos de presença fraternal e as recordarei com muito carinho por toda a minha vida. Desde os cuidados na infância, a atenção na adolescência às conversas acadêmicas na fase adulta, são pessoas que sempre me estenderam a mão e abriram o seu coração. Vocês, dindos, e ao meu querido primo‐irmão Juliano, o meu muito obrigado e a certeza de que este documento também tem palavras de vosso punho. Na UCPel, é impossível não lembrar dos meus queridos professores que me incentivaram a começar e seguir no mundo da investigação e não desistir das Ciências Biológicas – Ricardo, nem tudo é genética! Graça e Gilberto, que me acolhisteis no Laboratório de Genética da Universidade onde tanto aprendi. Ao técnico Abilio, tua filosofia é mais que um poema, é um ensinamento de viver, em memória, agradeço‐te. Lu, minha professora de bioquímica, diretora e minha amiga: participaste em todas as fases desta caminhada e sabes o árduo que é seguir adiante sendo um little alien fora das fronteiras. Resumindo, dizem que é medíocre o aluno que não supera seu professor; dado o panorama, vejo complicado que o consiga. Obrigado, mestres! Por fin, y tras una pequeña vuelta al mundo, llego al CNIO el 2004 como estudiante de verano y fui acogido como el brasileño atípico que, aunque con nivel ‐1 de castellano, me sobraban sonrisas dado que no me enteraba de mucho. En el mismo año vuelvo a Brasil, concluyo la carrera y una vez más, regreso al CNIO, pero ahora con la incumbencia de una tesis doctoral por desarrollar. De ahí, las descubiertas, muchísimo más positivas que negativas – empecé bien, ¡ostras! Me ha tocado la Ana Osorio ¿Qué pasará? Entre extracciones de ARN, amplificaciones, buff, el mundo de las pipetas me fascinaba y poco a poco, iba haciendo parte y buceando por el nuevo mundo de la biología molecular y de los micro…qué? Sí, microarrays.
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  • Childhood Onset Limb-Girdle Muscular Dystrophies in the Aegean Part of Turkey
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