Myeloproliferative neoplasms are clonal diseases of hematopoietic stem cells characterized by myeloid hyperplasia and increased risk of developing acute myeloid leukemia. Myeloproliferative neoplasms are caused, as any other malignancy, by genetic defects that culminate in the neoplastic phenotype. In the past six years, since the identification of JAK2V617F, we have experienced a substantial increase in our knowledge about the genetic mechanisms involved in the genesis of myeloproliferative neoplasms. Mutations described in several genes have revealed a considerable degree of molecular homogeneity between different subtypes of myeloproliferative neoplasms. At the same time, the molecular differences between each subtype have become clearer. While mutations in several genes, such as JAK2, myeloproliferative leukemia (MPL) and LNK have been validated in functional assays or animal models as causative mutations, the roles of other recurring mutations in the development of disease, such as TET2 and ASXL1 remain to be elucidated. In this review we will examine the most prevalent recurring gene mutations found in myeloproliferative neoplasms and their molecular consequences.

O câncer colorretal (CCR) é a terceira neoplasia mais freqüente no mundo. A mortalidade persiste inalterada nos últimos 50 anos a despeito dos avanços obtidos em diagnóstico e tratamento. Significativa parcela dos doentes se apresenta com tumores em estágio avançado ou incuráveis de onde se depreende a necessidade de rastreamento dos pacientes com lesões pré-malignas (pólipos adenomatosos) como resultado de herança genética ou idade, e de vigilância dos portadores de doença inflamatória intestinal de longa evolução. Na medida em que existem diferentes grupos de risco identificáveis para CCR e diferentes estratégias para o rastreamento, há que se determinar o protocolo de triagem capaz de oferecer maior relação custo-benefício. Uma vez que o objetivo das técnicas de rastreamento é diminuir a morbi-mortalidade da população analisada, o presente trabalho objetiva conhecer, sob essa perspectiva, os resultados dos estudos disponíveis até o momento para o rastreamento do CCR. Os principais métodos de rastreamento incluem, isoladamente ou em associação, o emprego da pesquisa de sangue oculto nas fezes, a sigmoidoscopia e o exame colonoscópico. As evidências de literatura a respeito dos métodos de rastreamento para os diversos grupos de risco específicos são insuficientes e, freqüentemente, não envolvem estudos controlados. A necessidade de realização desses estudos associada ao progresso nos estudos de genética molecular resultará em maior eficácia e menor custo associados ao rastreamento do CCR.

Colorectal cancer (CRC) is the third most common cancer in the world, and mortality has remained the same for the past 50 years, despite advances in diagnosis and treatment. Because significant numbers of patients present with advanced or incurable stages, patients with pre-malignant lesions (adenomatous polyps) that occur as result of genetic inheritance or age should be screened, and patients with long-standing inflammatory bowel disease should undergo surveillance. There are different risk groups for CRC, as well as different screening strategies. It remains to be determined which screening protocol is the most cost-effective for each risk catagory. The objective of screening is to reduce morbidity and mortality in a target population. The purpose of this review is to analyze the results of the published CRC screening studies, with regard to the measured reduction of morbidity and mortality, due to CRC in the studied populations, following various screening procedures. The main screening techniques, used in combination or alone, include fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy. Evidence from the published literature on screening methods for specific risk groups is scanty and frequently does not arise from controlled studies. Nevertheless, data from these studies, combined with recent advances in molecular genetics, certainly lead the way to greater efficacy and lower cost of CRC screening.