Different Genetic Signatures of SCLC...
Small-cell lung cancer (SCLC) is the malignancy most frequently associated with paraneoplastic neurological syndromes (PNS) and can trigger different antibody responses against intracellular (Hu) or neuronal surface (GABABR) antigens. Our aim was to clarify whether the genomic and transcriptomic features of SCLC are different in patients with anti-GABABR or anti-Hu PNS compared with SCLC without PNS.
A total of 76 SCLC tumor samples were collected: 34 anti-Hu, 14 anti-GABABR, and 28 SCLC without PNS. The study consisted of 4 steps: (1) pathological confirmation; (2) next generation sequencing using a panel of 98 genes, including those encoding the autoantibodies targets ELAVL1-4, GABBR1-2, and KCTD16; (3) genome-wide copy number variation (CNV); and (4) whole-transcriptome RNA sequencing.
SCLC genetic and transcriptomic features differentiate anti-GABABR, anti-Hu, and non-PNS tumors. The role of KCTD16 appears to be pivotal in the tumor immune tolerance breakdown of anti-GABABR PNS. ANN NEUROL 2023;94:1102–1115
