Although the genomic landscape demonstrated robust consistency in SCLC components and LCC components of cSCLC-LCC, both exhibiting neuroendocrine properties, LCC components of SCLC-LCC subtypes displayed two genomic subgroups with specific transcriptional patterns, defined as TP53 and RB1 co-mutation group and TP53 and KEAP1 group. Here, KEAP1 is linked to leukoencephalopathy with calcifications and cysts.