Open AccessPrediction and characterization of diffuse large B-cell lymphoma cell-of-origin subtypes using targeted sequencing
Author(s) -
Sally E. Trabucco,
Ethan Sokol,
Sophia L. Maund,
Jay A. Moore,
Garrett M. Frampton,
Lee A. Albacker,
Mikkel Z. Oestergaard,
Jeffrey M. Venstrom,
Laurie H. Sehn,
Christopher R. Bolen
Publication year - 2021
Publication title -
future oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.857
H-Index - 72
eISSN - 1744-8301
pISSN - 1479-6694
DOI - 10.2217/fon-2021-0370
Subject(s) - exome sequencing , somatic cell , dna sequencing , germinal center , carcinogenesis , diffuse large b cell lymphoma , biology , ion semiconductor sequencing , computational biology , cell of origin , germline mutation , genetics , cell , dna , mutation , gene , b cell , antibody , chemotherapy
The aim of the present study was to determine cell of origin (COO) from a platform using a DNA-based method, COO DNA classifier (COODC). A targeted exome-sequencing platform that applies the mutational profile of a sample was used to classify COO subtype. Two major mutational signatures associated with COO were identified: Catalogue of Somatic Mutations in Cancer (COSMIC) signature 23 enriched in activated B cell (ABC) and COSMIC signature 3, which suggested increased frequency in germinal center B cell (GCB). Differential mutation signatures linked oncogenesis to mutational processes during B-cell activation, confirming the putative origin of GCB and ABC subtypes. Integrating COO with comprehensive genomic profiling enabled identification of features associated with COO and demonstrated the feasibility of determining COO without RNA.