Detalle Publicación

Strategy for identification of a potential inherited leukemia predisposition in a 299 patient's cohort with tumor-only sequencing data

Autores: Aguilera-Diaz, A.; Larráyoz Ilundáin, María José; Palomino-Echeverria, S.; Vázquez Urio, Iria; Ariceta, B.; Mañú Arruti, Amagoia; Blasco-Iturri, Z.; Bernal del Castillo, T.; Olivares Salaverri, M.; Olave-Rubio, M. T.; Rifón Roca, José Juan; Alfonso Piérola, Ana; Prosper Cardoso, Felipe; Fernández Mercado, Marta (Autor de correspondencia); Calasanz Abinzano, María José
Título de la revista: LEUKEMIA RESEARCH
ISSN: 0145-2126
Volumen: 95
Fecha de publicación: 2020
Myeloid neoplasms (MN) are usually sporadic late-onset cancers; nevertheless, growing evidence suggests that similar to 5% of the cases could emerge as a consequence of inherited predisposition. Distinguishing somatic from germline variants is of vital importance, in order to establish an appropriate individualized management and counsel the patients and their relatives. Since many of the genes associated with myeloid neoplasm germline predisposition (MNGP) are also affected in sporadic MN, we intended to design a strategy to identify potentially inherited variants in a tumor only NGS panel in a cohort of 299 patients with a variety of MN. We considered as indicative of potential inherited origin, variants detected in BM sample at a similar to 50% VAF classified as pathogenic, likely pathogenic or of unknown significance detected in MNGP-related genes. A total of 104 suspicious variants from 90 patients were filtered-in in tumor samples. Mutational patterns, follow-up data, and sequencing of a range of non-myeloid tissues were used for narrowing down the list of suspicious variants, and ultimately discriminate their nature. Our data supports the importance of considering variants found upon tumor-only sequencing as potentially of germline origin, and we offer a pipeline to define the nature of the variants.