Comprehensive Analysis of Germline Variants in Mexican Patients with Hereditary Breast and Ovarian Cancer Susceptibility
| Autor: | Víctor Hugo Garzón Barrientos, Luis A. Herrera, Lizbeth García Esquivel, Ernesto Arturo Rojas Jiménez, Verónica Fragoso Ontiveros, Cecilia Frecha, Oscar Moreno García, Perla Karina Espino Silva, Gabriela Torres Mejia, Rosalía Quezada Urban, Luis I. Terrazas, Andrea Figueroa Morales, Luis Enrique Romero Cruz, Javier Oliver, María Patricia Rojo Castillo, Felipe Vaca Paniagua, Virginia Jan, Clara Estela Díaz Velásquez, Jorge Haro-Santa Cruz, Michael Dean, Pablo Ruiz Flores, Rosa María Álvarez Gómez, Isabelle Romieu, Claudia Fabiola Méndez Catalá, Yolanda I. Chirino, Héctor Martínez Gregorio, Hector Lopez, Fernando Rodríguez León, Rina Gitler, Iván Delgado Enciso, Sandra Perdomo, Max Sirota Toporek |
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| Přispěvatelé: | Perdomo Lara, Sandra Janneth [0000-0002-4429-3760] |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research BRCA1/2 Neoplasias ováricas Disease lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine Breast cancer gene panel Locus heterogeneity Genetic screening Medicine Allele Family history pathogenic variants Gene Hereditary breast cancer Genetics business.industry massive parallel sequencing Cancer hereditary breast cancer Massive parallel sequencing genetic screening lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Síndromes neoplásicos hereditarios 030104 developmental biology Oncology 030220 oncology & carcinogenesis Neoplasias de la mama business Ovarian cancer |
| Zdroj: | Cancers Volume 10 Issue 10 Repositorio U. El Bosque Universidad El Bosque instacron:Universidad El Bosque Cancers, Vol 10, Iss 10, p 361 (2018) |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers10100361 |
| Popis: | Hereditary breast and ovarian cancer syndrome (HBOC) represents 5–10% of all patients with breast cancer and is associated with high-risk pathogenic alleles in BRCA1/2 genes, but only for 25% of cases. We aimed to find new pathogenic alleles in a panel of 143 cancer-predisposing genes in 300 Mexican cancer patients with suspicion of HBOC and 27 high-risk patients with a severe family history of cancer, using massive parallel sequencing. We found pathogenic variants in 23 genes, including BRCA1/2. In the group of cancer patients 15% (46/300) had a pathogenic variant 11% (33/300) harbored variants with unknown clinical significance (VUS) and 74% (221/300) were negative. The high-risk group had 22% (6/27) of patients with pathogenic variants, 4% (1/27) had VUS and 74% (20/27) were negative. The most recurrent mutations were the Mexican founder deletion of exons 9-12 and the variant p.G228fs in BRCA1, each found in 5 of 17 patients with alterations in this gene. Rare VUS with potential impact at the protein level were found in 21 genes. Our results show for the first time in the Mexican population a higher contribution of pathogenic alleles in other susceptibility cancer genes (54%) than in BRCA1/2 (46%), highlighting the high locus heterogeneity of HBOC and the necessity of expanding genetic tests for this disease to include broader gene panels. |
| Databáze: | OpenAIRE |
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