Publication
Cell-free DNA methylation-defined prognostic subgroups in small-cell lung cancer identified by leukocyte methylation subtraction.
Journal Paper/Review - Nov 4, 2022
Ul Haq Sami, Schmid Sabine, Aparnathi Mansi K, Hueniken Katrina, Zhan Luna Jia, Sacdalan Danielle, Li Janice J N, Meti Nicholas, Patel Devalben, Cheng Dangxiao, Philip Vivek, Tsao Ming S, Cabanero Michael, de Carvalho Daniel, Liu Geoffrey, Bratman Scott V, Lok Benjamin H
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Brief description/objective
Small-cell lung cancer (SCLC) methylome is understudied. Here, we comprehensively profile SCLC using cell-free methylated DNA immunoprecipitation followed by sequencing (cfMeDIP-seq). Cell-free DNA (cfDNA) from plasma of 74 patients with SCLC pre-treatment and from 20 non-cancer participants, genomic DNA (gDNA) from peripheral blood leukocytes from the same 74 patients, and 7 accompanying circulating tumor cell-derived xenografts (CDXs) underwent cfMeDIP-seq. Peripheral blood leukocyte methylation (PRIME) subtraction to improve tumor specificity. SCLC cfDNA methylation is distinct from non-cancer but correlates with CDX tumor methylation. PRIME and k-means consensus identified two methylome clusters with prognostic associations that related to axon guidance, neuroactive ligand-receptor interaction, pluripotency of stem cells, and differentially methylated at long noncoding RNA and other repeats features. We comprehensively profiled the SCLC methylome in a large patient cohort and identified methylome clusters with prognostic associations. Our work demonstrates the potential of liquid biopsies in examining SCLC biology encoded in the methylome.