Assuntos
Neoplasias Encefálicas , Neoplasias Colorretais , Reparo de Erro de Pareamento de DNA/genética , Síndromes Neoplásicas Hereditárias , Adolescente , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Criança , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , DNA Polimerase II/genética , DNA Polimerase III/genética , Diagnóstico Diferencial , Aconselhamento Genético , Mutação em Linhagem Germinativa , Guias como Assunto , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Síndrome de Li-Fraumeni/psicologia , Lúpus Eritematoso Sistêmico/genética , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/terapia , Países Baixos , Proteínas de Ligação a Poli-ADP-Ribose/genética , Vacinação , Adulto JovemRESUMO
Tackling the topic of genetic predisposition to childhood cancer requires close co-operation between pathologists, pediatric oncologists, and human geneticists. It is not just about the precise diagnosis and the most effective treatment of the cancer, but also to prevent further cancerous diseases for those affected and also their family members. On the basis of examples such as Li-Fraumeni syndrome, constitutional mismatch repair deficiency (CMMRD), medullo- and neuroblastoma, as well as hematological neoplasias, we will discuss the criteria for tumor predisposition genetic syndromes, the relationship between somatic and germline variants, and the immediate clinical consequences. In some cases, the diagnosis of a genetic tumor predisposition syndrome has immediate consequences for the treatment, e.â¯g. to avoid radiotherapy for Li-Fraumeni syndrome, which would otherwise significantly increase the probability of secondary, independent tumors. Predictive diagnostics can be offered to identify the family members who carry the pathogenic variant. Because of their increased tumor risk, they should be integrated into cancer surveillance programs. Evidence-based data show that this significantly improves overall survival.
Assuntos
Neoplasias Encefálicas , Neoplasias Colorretais , Predisposição Genética para Doença , Neoplasias Hematológicas , Síndromes Neoplásicas Hereditárias , Criança , Mutação em Linhagem Germinativa , HumanosAssuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Mutação em Linhagem Germinativa , Heterozigoto , Leucemia Mieloide Aguda/complicações , Modelos Biológicos , Síndromes Mielodisplásicas/genética , Adolescente , Feminino , Humanos , Cariotipagem , Masculino , Síndromes Mielodisplásicas/complicações , LinhagemRESUMO
Combining fluorescence R-banding, fluorescence in situ hybridization and spectral karyotyping allowed us to precisely define chromosomal breakpoints, gains, losses and a newly detected amplification in the human mantle cell lymphoma (MCL) cell line GRANTA-519. GRANTA-519 is characterized by the t(11;14)(q13;q32) resulting in overexpression of cyclin D1, a key player in cell cycle control. Hitherto unresolved complex rearrangements involve 1p, 1q, 3cen, 9p, 11q, 12p, 12q, 16p, 17p, and 18cen. Moreover, a 4- to 6-fold gain of sequences on 18q leads to a low-level amplification of the BCL2 gene and to an overexpression of the BCL2 protein. These results provide the basis for the identification of not only candidate oncogenes responsible for MCL in gained regions, but also for the identification of putative tumor suppressor genes in commonly deleted regions like 1p22, which would eventually enable functional studies of these genes.