Cell-free DNA methylation-defined prognostic subgroups in small-cell lung cancer identified by leukocyte methylation subtraction.

Publikation

Cell-free DNA methylation-defined prognostic subgroups in small-cell lung cancer identified by leukocyte methylation subtraction.

Wissenschaftlicher Artikel/Review - 04.11.2022

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

Zitation

Ul Haq S, Schmid S, Aparnathi M, Hueniken K, Zhan L, Sacdalan D, Li J, Meti N, Patel D, Cheng D, Philip V, Tsao M, Cabanero M, de Carvalho D, Liu G, Bratman S, Lok B. Cell-free DNA methylation-defined prognostic subgroups in small-cell lung cancer identified by leukocyte methylation subtraction. iScience 2022; 25:105487.

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

iScience 2022; 25

Veröffentlichungsdatum

04.11.2022

eISSN (Online)

2589-0042

Seiten

105487

Kurzbeschreibung/Zielsetzung

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.