Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Sistema de Registros , Transplante de Células-Tronco , Adulto , Idoso , Autoenxertos , Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Dinamarca/epidemiologia , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Taxa de Sobrevida , Talidomida/administração & dosagemRESUMO
Both environmental and host factors influence risk of cutaneous melanoma (CM), and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma.
Assuntos
Genes Neoplásicos/genética , Predisposição Genética para Doença/genética , Testes Genéticos/normas , Melanoma/epidemiologia , Melanoma/genética , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/genética , Quinase 4 Dependente de Ciclina , Inibidor p16 de Quinase Dependente de Ciclina/genética , Dinamarca/epidemiologia , Mutação em Linhagem Germinativa/genética , Humanos , Fator de Transcrição Associado à Microftalmia , Receptor Tipo 1 de Melanocortina , Proteínas Supressoras de Tumor , Ubiquitina TiolesteraseRESUMO
BACKGROUND: Children with Down syndrome (DS) have an increased risk for acute lymphoblastic leukemia (ALL). Although previous studies have shown that DS-ALL differs clinically and genetically from non-DS-ALL, much remains to be elucidated as regards genetic and prognostic factors in DS-ALL. METHODS: To address clinical and genetic differences between DS-ALL and non-DS-ALL and to identify prognostic factors in DS-ALL, we ascertained and reviewed all 128 pediatric DS-ALL diagnosed in the Nordic countries between 1981 and 2010. Their clinical and genetic features were compared with those of the 4,647 B-cell precursor (BCP) ALL cases diagnosed during the same time period. RESULTS: All 128 DS-ALL were BCP ALL, comprising 2.7% of all such cases. The 5-year event-free survival (EFS) and overall survival (OS) were significantly (P = 0.026 and P = 0.003, respectively) worse for DS-ALL patients with white blood cell counts ≥50 × 109/l. The age distributions varied between the DS and non-DS cases, with age peaks at 2 and 3 years, respectively; none of the DS patients had infant ALL (P = 0.029). The platelet counts were lower in the DS-ALL group (P = 0.005). Abnormal karyotypes were more common in non-DS-ALL (P < 0.0001), and there was a significant difference in the modal number distribution, with only 2% high hyperdiploid DS-ALL cases (P < 0.0001). The 5-year EFS and 5-year OS were significantly worse for DS-ALL (0.574 and 0.691, respectively) compared with non-DS-ALL (0.783 and 0.894, respectively) in the NOPHO ALL-1992/2000 protocols (P < 0.001). CONCLUSIONS: The present study adds further support for genetic and clinical differences between DS-ALL and non-DS-ALL.
