RESUMEN
BACKGROUND: Hereditary cancer predisposition syndromes are responsible for approximately 5-10% of all diagnosed cancer cases. In the past, single-gene analysis of specific high risk genes was used for the determination of the genetic cause of cancer heritability in certain families. The application of Next Generation Sequencing (NGS) technology has facilitated multigene panel analysis and is widely used in clinical practice, for the identification of individuals with cancer predisposing gene variants. The purpose of this study was to investigate the extent and nature of variants in genes implicated in hereditary cancer predisposition in individuals referred for testing in our laboratory. METHODS: In total, 1197 individuals from Greece, Romania and Turkey were referred to our laboratory for genetic testing in the past 4 years. The majority of referrals included individuals with personal of family history of breast and/or ovarian cancer. The analysis of genes involved in hereditary cancer predisposition was performed using a NGS approach. Genomic DNA was enriched for targeted regions of 36 genes and sequencing was carried out using the Illumina NGS technology. The presence of large genomic rearrangements (LGRs) was investigated by computational analysis and Multiplex Ligation-dependent Probe Amplification (MLPA). RESULTS: A pathogenic variant was identified in 264 of 1197 individuals (22.1%) analyzed while a variant of uncertain significance (VUS) was identified in 34.8% of cases. Clinically significant variants were identified in 29 of the 36 genes analyzed. Concerning the mutation distribution among individuals with positive findings, 43.6% were located in the BRCA1/2 genes whereas 21.6, 19.9, and 15.0% in other high, moderate and low risk genes respectively. Notably, 25 of the 264 positive individuals (9.5%) carried clinically significant variants in two different genes and 6.1% had a LGR. CONCLUSIONS: In our cohort, analysis of all the genes in the panel allowed the identification of 4.3 and 8.1% additional pathogenic variants in other high or moderate/low risk genes, respectively, enabling personalized management decisions for these individuals and supporting the clinical significance of multigene panel analysis in hereditary cancer predisposition.
Asunto(s)
Neoplasias de la Mama/genética , Neoplasias Colorrectales/genética , Pruebas Genéticas/métodos , Mutación , Síndromes Neoplásicos Hereditarios/genética , Neoplasias Ováricas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios de Cohortes , Femenino , Genes BRCA1 , Genes BRCA2 , Predisposición Genética a la Enfermedad , Variación Genética , Grecia , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Masculino , Persona de Mediana Edad , Linaje , Rumanía , Turquía , Adulto JovenRESUMEN
BACKGROUND/AIM: The use of multi-gene panels for germline testing in breast cancer enables the estimation of cancer risk and guides risk-reducing management options. The aim of this study was to present data that demonstrate the different levels of actionability for multi-gene panels used in genetic testing of breast cancer patients and their family members. MATERIALS AND METHODS: We performed an analysis in our clinical database to identify breast cancer patients undergoing genetic testing. We reviewed positive results in respect of risk estimation and management, cascade family testing, secondary findings and information for treatment decision-making. RESULTS: A total of 415 positive test reports were identified with 57.1%, 18.1%, 10.8% and 13.5% of individuals having pathogenic/likely pathogenic variants in high, moderate, low and with insufficient evidence for breast cancer risk genes, respectively. Six point seven percent of individuals were double heterozygotes. CONCLUSION: Germline findings in 92% of individuals are linked to evidence-based treatment information and risk estimates for predisposition to breast and/or other cancer types. The use of germline findings for treatment decision making expands the indication of genetic testing to include individuals that could benefit from targeted treatments.
Asunto(s)
Neoplasias de la Mama Masculina/epidemiología , Neoplasias de la Mama/epidemiología , Análisis Mutacional de ADN/normas , Pruebas Genéticas/normas , Mutación de Línea Germinal , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/antagonistas & inhibidores , Biomarcadores de Tumor/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/prevención & control , Neoplasias de la Mama Masculina/tratamiento farmacológico , Neoplasias de la Mama Masculina/genética , Neoplasias de la Mama Masculina/prevención & control , Toma de Decisiones Clínicas/métodos , Familia , Femenino , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida/métodos , Medicina de Precisión/métodos , Medicina de Precisión/normas , Estudios Retrospectivos , Medición de Riesgo/métodos , Medición de Riesgo/normas , Adulto JovenRESUMEN
Although the metastases from extra- abdominal tumors to the small bowel are rare, cutaneous melanoma is the most common source. A 78 year old man with occult intestinal bleeding due to malign melanoma of the small bowel was admitted to our clinics. The patient was managed successfully by small bowel resection with end to end anastomosis. Patient is alive three months after the surgery and is in pretty good condition.