Relapse timing is associated with distinct evolutionary dynamics in DLBCL.

Autor: Hilton LK; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada.; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Ngu HS; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada., Collinge B; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Dreval K; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.; Canada's Michael Smith Genome Sciences Centre, BC Cancer Research Institute, Vancouver, BC, Canada., Ben-Neriah S; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada., Rushton CK; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Wong JCH; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada., Cruz M; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Roth A; Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, BC, Canada., Boyle M; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada., Meissner B; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada., Slack GW; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Farinha P; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Craig JW; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Gerrie AS; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Freeman CL; Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL., Villa D; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Crump M; Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada., Shepherd L; Canadian Cancer Trials Group, Queens University, Kingston, ON, Canada.; Department of Medicine, Queens University, Kingston, ON, Canada., Hay AE; Canadian Cancer Trials Group, Queens University, Kingston, ON, Canada.; Department of Medicine, Queens University, Kingston, ON, Canada., Kuruvilla J; Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada., Savage KJ; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Kridel R; Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada., Karsan A; Canada's Michael Smith Genome Sciences Centre, BC Cancer Research Institute, Vancouver, BC, Canada., Marra MA; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada.; Canada's Michael Smith Genome Sciences Centre, BC Cancer Research Institute, Vancouver, BC, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada., Sehn LH; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Steidl C; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Morin RD; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada.; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.; Canada's Michael Smith Genome Sciences Centre, BC Cancer Research Institute, Vancouver, BC, Canada., Scott DW; Centre for Lymphoid Cancer, BC Cancer Research Institute, Vancouver, BC, Canada.; Division of Medical Oncology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Jazyk: angličtina
Zdroj: MedRxiv : the preprint server for health sciences [medRxiv] 2023 Mar 08. Date of Electronic Publication: 2023 Mar 08.
DOI: 10.1101/2023.03.06.23286584
Abstrakt: Diffuse large B-cell lymphoma (DLBCL) is cured in over 60% of patients, but outcomes are poor for patients with relapsed or refractory disease (rrDLBCL). Here, we performed whole genome/exome sequencing (WGS/WES) on tumors from 73 serially-biopsied patients with rrDLBCL. Based on the observation that outcomes to salvage therapy/autologous stem cell transplantation are related to time-to-relapse, we stratified patients into groups according to relapse timing to explore the relationship to genetic divergence and sensitivity to salvage immunochemotherapy. The degree of mutational divergence increased with time between biopsies, yet tumor pairs were mostly concordant for cell-of-origin, oncogene rearrangement status and genetics-based subgroup. In patients with highly divergent tumors, several genes acquired exclusive mutations independently in each tumor, which, along with concordance of genetics-based subgroups, suggests that the earliest mutations in a shared precursor cell constrain tumor evolution. These results suggest that late relapses commonly represent genetically distinct and chemotherapy-naïve disease.
Databáze: MEDLINE