Alterações genéticas no cancro do pulmão: Avaliação das limitações ao seu uso na rotina clínica

Genetic alterations in lung cancer: Assessing limitations in routine clinical use

 

Joana Espiga Macedo¹

Inês A M Barbosa^2,3

Sandra Rebelo^1,4

Conceição Souto de Moura^1,5

Luís Teixeira da Costa^2,6

Venceslau Hespanhol^1,7

 

Resumo

O cancro do pulmão é a causa mais frequente de mortalidade por cancro no mundo, sendo responsável por cerca de 1,1 milhões de mortes por ano. A sobrevivência média dos doentes é geralmente curta, por a doença se encontrar em estádios avançados na altura do diagnóstico, mas também devido à falta de eficácia dos tratamentos disponíveis. O advento da genética molecular dos tumores trouxe consigo a possibilidade de modificar esta situação, quer através do refinamento do diagnóstico, quer da identificação de alvos terapêuticos específicos, quer sobretudo por – pelo menos em teoria – permitir o diagnóstico precoce da doença. No entanto, e apesar de numerosos trabalhos terem já demonstrado a utilidade das técnicas da genética molecular no estudo do cancro do pulmão, o seu uso na rotina clínica em Portugal tem sido limitado. No presente estudo, utilizou-se a pesquisa de mutações no anti-oncogene p53 em amostras clínicas de doentes com diagnóstico de cancro do pulmão como método para identificar as dificuldades práticas à integração da genética molecular na rotina clínica. Os resultados obtidos sugerem que o principal factor limitante a essa integração é a obtenção de amostras de ADN de qualidade, um problema que pode ser superado pela alteração das práticas correntes de recolha de amostras.

Palavras-chave: Cancro, pulmão, clínica, genética molecular, mutação, p53.

 

Abstract

Lung cancer is the most frequent cause of cancer mortality worldwide, responsible for approximately 1.1 million deaths per year. Median survival is short, both as most tumours are diagnosed at an advanced stage and because of the limited efficacy of available treatments. The development of tumour molecular genetics carries the promise of altering this state of affairs, as it should lead to a more precise classification of tumours, identify specific molecular targets for therapy and, above all, allow the development of new methods for early diagnosis. Despite numerous studies demonstrating the usefulness of molecular genetic techniques in the study of lung cancer, its routine clinical use in Portugal has, however, been limited. In this study, we used a p53 mutation screen in multiple clinical samples from a series of lung cancer patients to attempt to identify the main practical limitations to the integration of molecular genetics in routine clinical practice. Our results suggest that the main limiting factor is the availability of samples with good quality DNA; a problem that could be overcome by alterations in common sample collection and storage procedures.

Key-words: Cancer, lung, clinical, molecular genetics, mutation, p53.

 

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¹ Faculdade de Medicina da Universidade do Porto / University of Porto Faculty of Medicine

² IPATIMUP

³ Faculdade de Ciências da Universidade do Porto / University of Porto Faculty of Science

⁴ Serviço de Histologia, Hospital de S. João / Hospital de S. João, Histology Unit

⁵ Serviço de Anatomia Patológica, Hospital de S. João / Hospital de S. João, Anatomic Pathology Unit

⁶ ICAM, Universidade de Évora / ICAM, University of Évora

⁷ Serviço de Pneumologia, Hospital de S. João / Hospital de S. João, Pulmonolgy Unit

 

Recebido para publicação/received for publication: 06.10.31

Aceite para publicação/accepted for publication: 06.12.12