DNA damage response-related alterations define the genetic background of patients with chronic lymphocytic leukemia and chromosomal gains

Experimental Hematology
María Hernández-SánchezJesús María Hernández-Rivas

Abstract

The presence of chromosomal gains other than trisomy 12 suggesting a hyperdiploid karyotype is extremely rare in chronic lymphocytic leukemia (CLL) and is associated with a dismal prognosis. However, the genetic mechanisms and mutational background of these patients have not been fully explored. To improve our understanding of the genetic underpinnings of this subgroup of CLL, seven CLL patients with several chromosomal gains were sequenced using a next-generation sequencing (NGS)-targeted approach. The mutational status of 54 genes was evaluated using a custom-designed gene panel including recurrent mutated genes observed in CLL and widely associated with CLL pathogenesis. A total of 21 mutations were detected; TP53 (42.8%), ATM (28.5%), SF3B1 (28.5%), and BRAF (28.5%) were the most recurrently mutated genes. Of these mutations, 61.9% were detected in genes previously associated with a poor prognosis in CLL. Interestingly, five of the seven patients exhibited alterations in TP53 or ATM (deletion and/or mutation), genes involved in the DNA damage response (DDR), which could be related to a high genetic instability in this subgroup of patients. In conclusion, CLL patients with several chromosomal gains exhibit high genetic insta...Continue Reading

Citations

Oct 17, 2019·Frontiers in Genetics·Adrián Mosquera OrgueiraJosé Luis Bello López
Jul 29, 2020·International Journal of Cancer. Journal International Du Cancer·Claudia Pérez-CarreteroJesús-María Hernández-Rivas
Feb 27, 2021·Clinical and Translational Medicine·Miguel Quijada-ÁlamoJesús-María Hernández-Rivas
Jun 3, 2021·Diagnostics·Claudia Pérez-CarreteroJesús María Hernández-Rivas
Jul 11, 2021·Blood Cancer Journal·Miguel Quijada-ÁlamoJesús-María Hernández-Rivas

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