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  • 1
    Online Resource
    Online Resource
    Risk of metastasis in BRCA2 carriers diagnosed with triple‐negative breast cancer
    Wiley ; 2023
    In:  Cancer Medicine Vol. 12, No. 15 ( 2023-08), p. 16129-16141
    Details
    In: Cancer Medicine, Wiley, Vol. 12, No. 15 ( 2023-08), p. 16129-16141
    Abstract: Triple‐negative breast cancer (TNBC) is the neoplasia most associated with BRCA1 germline pathogenic variants (PV) and is more likely to develop metastases than the other breast cancer (BC) subtypes, mainly in the lungs and the central nervous system (CNS). Recently, BRCA2 carriers were shown to have a higher risk for developing CNS metastases. However, the patterns of recurrence and metastases of BRCA2 carriers with TNBC are unknown. Methods TNBC patient data attending the A.C. Camargo Cancer Center, from 1998 through 2020, were verified either by medical records or by BRCA1/2 genetic testing carried out. Multivariable logistic regression models were fit to the data to assess the independent factors for bone and CNS metastases. Adjustment was done using all independent variables with p 〈 0.2 in the univariable Cox model to describe the relationship between the independent variables until time of death. Results A total of 388 TNBC patients were evaluated. We identified PV in BRCA1/2 genes in 21% (82/388), being 17.7% (69/388) in BRCA1 and only 3.3% (13/388) in BRCA2 . A total of 120 patients (31%) developed distant metastases. Bone or CNS metastases were observed in 40% and 60% of BRCA2 PV carriers ( p = 0.155), respectively. The BRCA2 carriers tended to have a higher likelihood of developing bone metastases (OR, 4.06; 95% CI, 0.82–20.01; p = 0.085), when compared to BRCA1 carriers (OR, 0.6; 95% CI, 0.12–2.87; p = 0.528). BRCA2 carriers had an OR of 1.75 (95% CI, 0.33–9.14; p = 0.503) for CNS metastasis development, while BRCA1 carriers had an OR of 0.72 (95% CI, 0.23–2.23; p = 0.574). Conclusions Patients with TNBC and PV in the BRCA2 gene had higher frequencies of secondary bone involvement and CNS in the course of the disease. However, the BRCA2 PV did not represent an independent outcome predictor of metastases and overall survival. Efforts to increase the number of BRCA2 carriers among TNBC patients are crucial for determining their risk of developing bone and CNS metastases compared to BRCA2 noncarriers.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    URL: Article
    DOI: 10.1002/cam4.v12.15
    DOI: 10.1002/cam4.6267
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2659751-2
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  • 2
    Online Resource
    Online Resource
    Genetic Landscape of Male Breast Cancer
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 14 ( 2021-07-15), p. 3535-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 14 ( 2021-07-15), p. 3535-
    Abstract: Male breast cancer (MBC) is now considered molecularly different from female breast cancer (FBC). Evidence from studies indicates that common genetic and epigenetic features of FBC are not shared with those diagnosed in men. Genetic predisposition is likely to play a significant role in the tumorigenesis of this rare disease. Inherited germline variants in BRCA1 and BRCA2 account for around 2% and 10% of MBC cases, respectively, and the lifetime risk of breast cancer for men harboring BRCA1 and BRCA2 mutations is 1.2% and 6.8%. As for FBC, pathogenic mutations in other breast cancer genes have also been recently associated with an increased risk of MBC, such as PALB2 and CHEK2 mutations. However, while multigene germline panels have been extensively performed for BC female patients, the rarity of MBC has resulted in limited data to allow the understanding of the magnitude of risk and the contribution of recently identified moderate penetrance genes of FBC for MBC predisposition. This review gathers available data about the germline genetic landscape of men affected by breast cancer, estimated risk associated with these genetic variants, and current guidelines for clinical management.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13143535
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 3
    Online Resource
    Online Resource
    Avaliação de alterações germinativas em MUTYH em pacientes com câncer colorretal e mutação somática KRAS G12C
    Publicacoes Cientificas de Acesso Aberto e Editora LTDA ; 2022
    In:  Brazilian Journal of Case Reports Vol. 2, No. Suppl.1 ( 2022-07-25), p. 14-
    Details
    In: Brazilian Journal of Case Reports, Publicacoes Cientificas de Acesso Aberto e Editora LTDA, Vol. 2, No. Suppl.1 ( 2022-07-25), p. 14-
    Abstract: Introdução: A Polipose Associada ao gene MUTYH (MAP) é uma síndrome recessiva causada por mutações bialélicas em MUTYH, as quais inativam o gene e levam a uma alta ocorrência de transversões G:C à T:A, gerando a mutação KRAS c.34G 〉 T; G12C. A mutação ocorre em menos de 5% dos casos de câncer colorretal (CCR) esporádicos, mas é altamente frequente em CCR de pacientes MAP. Objetivo: O objetivo do estudo é avaliar a taxa de detecção de variantes germinativas patogênicas/provavelmente patogênicas em MUTYH em pacientes com CCR e mutação somática KRAS G12C. Metodologia: Avaliaremos 3 variantes patogênicas de MUTYH (p.Tyr179Cys, p.Gly396Asp e deleção dos éxons 4 a 16) por PCR multiplex, eletroforese e sequenciamento de nova geração (NGS). Pacientes com 1 variante em heterozigose serão submetidos ao sequenciamento completo do MUTYH. As características clínicas e anatomopatológicas dos pacientes serão correlacionadas com resultados que serão descritos estatisticamente. Resultados preliminares: Até o momento foram identificados 121 pacientes com CCR mutação KRAS c.34G 〉 T; G12C com média de idade de 59 anos, dos quais 51 apresentavam história familiar positiva (42,14%) e 46 apresentavam ao menos 1 pólipo (38,01%). Para 39 pacientes identificamos disponibilidade de material no Biobanco da instituição. Em análises prévias, avaliamos 9 pacientes com CCR antes dos 50 anos e identificamos 3 (33%) com alteração em MUTYH, sendo 2 com variantes patogênicas em ambos os alelos e 1 com uma variante patogênica e uma de significado incerto (VUS). Conclusão: Esperamos verificar se pacientes com CCR mutação somática KRAS G12C apresentam maior risco de detecção de variantes germinativas patogênicas no gene MUTYH, podendo-se utilizar dos resultados da detecção da mutação em KRAS como um teste pré-triagem para diagnóstico da MAP.
    Type of Medium: Online Resource
    ISSN: 2763-583X
    URL: Article
    DOI: 10.52600/2763-583X.bjcr.2022.2.Suppl.1.14
    Language: Unknown
    Publisher: Publicacoes Cientificas de Acesso Aberto e Editora LTDA
    Publication Date: 2022
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  • 4
    Online Resource
    Online Resource
    Prevalence and clinical implications of germline pathogenic variants in cancer predisposing genes in young patients across sarcoma subtypes
    BMJ ; 2023
    In:  Journal of Medical Genetics
    Details
    In: Journal of Medical Genetics, BMJ
    Abstract: Sarcomas are a rare and diverse group of cancers occurring mainly in young individuals for which an underlying germline genetic cause remains unclear in most cases. Methods Germline DNA from 177 children, adolescents and young adults with soft tissue or bone sarcomas was tested using multigene panels with 113 or 126 cancer predisposing genes (CPGs) to describe the prevalence of germline pathogenic/likely pathogenic variants (GPVs). Subsequent testing of a subset of tumours for loss of heterozygosity (LOH) evaluation was performed to investigate the clinical and molecular significance of these variants. Results GPVs were detected in 21.5% (38/177) of the patients (15.8% in children and 21.6% in adolescents and young adults), with dominant CPGs being altered in 15.2% overall. These variants were found in genes previously associated with the risk of developing sarcomas ( TP53 , RB1 , NF1 , EXT1/2 ) but also in genes where that risk is still emerging/limited ( ERCC2 , TSC2 and BRCA2 ) or unknown ( PALB2 , RAD50 , FANCM and others). The detection rates of GPVs varied from 0% to 33% across sarcoma subtypes and GPV carriers were more likely to present more than one primary tumour than non-carriers (21.1%×6.5%; p=0.012). Loss of the wild-type allele was detected in 48% of tumours from GPV carriers, mostly in genes definitively associated with sarcoma risk. Conclusion Our findings reveal that a high proportion of young patients with sarcomas presented a GPV in a CPG, underscoring the urgency of establishing appropriate genetic screening strategies for these individuals and their families.
    Type of Medium: Online Resource
    ISSN: 0022-2593 , 1468-6244
    URL: Article
    DOI: 10.1136/jmg-2023-109269
    RVK:
    WA 15000
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2009590-9
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association with MSH2 Germline Pathogenic Variants
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 7 ( 2020-07-09), p. 1848-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 7 ( 2020-07-09), p. 1848-
    Abstract: Lynch syndrome (LS) is a hereditary cancer-predisposing syndrome associated most frequently with epithelial tumors, particularly colorectal (CRC) and endometrial carcinomas (EC). The aim of this study was to investigate the relationship between sarcomas and LS by performing clinical and molecular characterization of patients presenting co-occurrence of sarcomas and tumors from the LS spectrum. We identified 27 patients diagnosed with CRC, EC, and other LS-associated tumors who had sarcomas in the same individuals or families. Germline genetic testing, mismatch repair (MMR) protein immunohistochemistry, microsatellite instability (MSI), and other molecular analyses were performed. Five LS patients presenting personal or family history of sarcomas were identified (3 MSH2 carriers and 2 MLH1), with 2 having Muir–Torre phenotypes. For two MSH2 carriers we confirmed the etiology of the sarcomas (one liposarcoma and two osteosarcomas) as LS-related, since the tumors were MSH2/MSH6-deficient, MSI-high, or presented a truncated MSH2 transcript. Additionally, we reviewed 43 previous reports of sarcomas in patients with LS, which revealed a high frequency (58%) of MSH2 alterations. In summary, sarcomas represent a rare clinical manifestation in patients with LS, especially in MSH2 carriers, and the analysis of tumor biological characteristics can be useful for definition of tumor etiology and novel therapeutic options.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12071848
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 6
    Online Resource
    Online Resource
    Avaliação molecular e fenotípica de indivíduos e famílias portadores da Síndrome de Neoplasia Hereditária Multilocus (MINAS)
    Publicacoes Cientificas de Acesso Aberto e Editora LTDA ; 2022
    In:  Brazilian Journal of Case Reports Vol. 2, No. Suppl.1 ( 2022-07-25), p. 28-
    Details
    In: Brazilian Journal of Case Reports, Publicacoes Cientificas de Acesso Aberto e Editora LTDA, Vol. 2, No. Suppl.1 ( 2022-07-25), p. 28-
    Abstract: Introdução: Uma pequena parcela dos pacientes portadores de síndromes de predisposição hereditária ao câncer (SPHC) apresenta variantes patogênicas em mais de um gene de predisposição ao câncer (GPC), condição recentemente descrita como síndrome de neoplasia hereditária multilocus (MINAS) e com implicações clínicas ainda desconhecidas. Objetivo: O presente estudo tem como objetivo descrever as características clínicas de pacientes/famílias com MINAS e avaliar características moleculares dos tumores desses indivíduos, buscando definir relações de etiologia entre variantes e tumores, efeitos sinérgicos e riscos modificados nesses indivíduos. Metodologia: Foi realizada coleta de dados clínicos, histopatológicos e de histórico familiar de 27 pacientes portadores de MINAS identificados na casuística do A.C.Camargo. Estão sendo realizadas análises de co-segregação em familiares com câncer e, em material tumoral, análises de perda de heterozigose (LoH) através de NGS de amplicon. Resultados: Observa-se um predomínio de pacientes mulheres (22/27) e com histórico de câncer de mama (14/27) e prevalência de síndrome de câncer de mama e ovário hereditários (HBOC). Os genes com variantes patogênicas/provavelmente patogênicas identificados em um maior número de pacientes foram: BRCA2 (13), MUTYH (6), BRCA1 (5), CHEK2 (5), TP53 (3). Sessenta e quatro por cento dos pacientes apresentam variantes em dois genes de herança autossômica dominante, 30% apresentaram 1 gene de herança autossômica dominante e 1 de autossômica recessiva (monoalélico) e 7% apresentaram variantes em dois genes de herança autossômica recessiva (monoalélico). Os resultados preliminares de perda de heterozigose demonstram que houve perda somática do alelo selvagem por deleção em 3 dos 5 tumores avaliados, nos genes BRCA1, BRCA2, ATM. Conclusão: Esperamos descrever as consequências fenotípicas clínicas e moleculares de um grupo raro de pacientes portadores de MINAS, colaborando para o conhecimento científico da área e contribuindo com o banco de dados de MINAS.
    Type of Medium: Online Resource
    ISSN: 2763-583X
    URL: Article
    DOI: 10.52600/2763-583X.bjcr.2022.2.Suppl.1.28
    Language: Unknown
    Publisher: Publicacoes Cientificas de Acesso Aberto e Editora LTDA
    Publication Date: 2022
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